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Mol Cell Biol, February 1998, p. 839-845, Vol. 18, No. 2
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activation of Protein Kinase C Triggers Its Ubiquitination and Degradationdagger

Zhimin Lu,1 David Liu,2 Armand Hornia,1 Wayne Devonish,1 Michele Pagano,2 and David A. Foster1,*

Department of Biological Sciences, Hunter College and the Graduate School of the City University of New York, New York, New York 10021,1 and Department of Pathology, New York University Medical Center, New York, New York 100162

Received 13 August 1997/Returned for modification 25 September 1997/Accepted 20 October 1997

    ABSTRACT
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Treatment of cells with tumor-promoting phorbol esters results in the activation but then depletion of phorbol ester-responsive protein kinase C (PKC) isoforms. The ubiquitin-proteasome pathway has been implicated in regulating the levels of many cellular proteins, including those involved in cell cycle control. We report here that in 3Y1 rat fibroblasts, proteasome inhibitors prevent the depletion of PKC isoforms alpha , delta , and varepsilon  in response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Proteasome inhibitors also blocked the tumor-promoting effects of TPA on 3Y1 cells overexpressing c-Src, which results from the depletion of PKC delta . Consistent with the involvement of the ubiquitin-proteasome pathway in the degradation of PKC isoforms, ubiquitinated PKC alpha , delta , and varepsilon  were detected within 30 min of TPA treatment. Diacylglycerol, the physiological activator of PKC, also stimulated ubiquitination and degradation of PKC, suggesting that ubiquitination is a physiological response to PKC activation. Compounds that inhibit activation of PKC prevented both TPA- and diacylglycerol-induced PKC depletion and ubiquitination. Moreover, a kinase-dead ATP-binding mutant of PKC alpha  could not be depleted by TPA treatment. These data are consistent with a suicide model whereby activation of PKC triggers its own degradation via the ubiquitin-proteasome pathway.

    INTRODUCTION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Tumor promotion by phorbol esters involves the selective amplification of cells previously mutated in an appropriate growth-stimulatory gene (3, 17). Phorbol esters exert their effects on the protein kinase C (PKC) family of genes, which consists of genes that encode at least nine distinct isoforms that are responsive to tumor-promoting phorbol esters (9). Phorbol esters first activate phorbol ester-responsive PKC isoforms, but upon prolonged treatment, these isoforms are proteolytically degraded (16). Using a cell culture model system in which cells overexpressing c-Src were transformed by phorbol ester treatment, we recently demonstrated that the tumor-promoting effect of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on these cells was due to the depletion of PKC delta  (7). These data suggested that PKC delta  may function as a tumor suppressor. Consistent with this hypothesis, PKC delta  was inactivated by tyrosine phosphorylation in cells transformed by v-Src (19) and v-Ras (2). Thus, regulation of PKC delta  at the level of activity and expression may be a very important cell growth control mechanism.

PKC alpha  has been reported to become ubiquitinated in response to bryostatin 1, an activator of PKC that prevents tumor promotion in mouse skin by TPA (6). The ubiquitin-proteasome pathway is a nonlysosomal degradation system that controls the timed destruction of cell cycle-regulatory proteins, including the tumor suppressor p53; the cyclin-dependent kinase inhibitor p27; the cyclins; the oncogene products c-Myc, c-Jun, and c-Fos; and the transcription factors NF-kappa B and E2F (reviewed in reference 13). This pathway involves the covalent tagging of proteins with ubiquitin, followed by proteasome-mediated degradation of tagged proteins. Conjugation of ubiquitin to substrate proteins requires three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). Both the E2 and E3 proteins belong to large families of proteins, and it is believed that different combinations of E2 proteins with different E3 ligases define a high substrate specificity. In this study, we have investigated the role of the ubiquitin-proteasome pathway in the downregulation of PKC isoforms in response to the tumor-promoting phorbol ester TPA.

    MATERIALS AND METHODS
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Abstract
Introduction
Materials & Methods
Results
Discussion
References

Cells and cell culture conditions. Rat 3Y1 cells or rat 3Y1 cells expressing either v-Src or c-Src were maintained in Dulbecco's modified Eagle medium supplemented with 10% bovine calf serum (HyClone). Cell cultures were made quiescent by growing them to confluence and then replacing the medium with fresh medium containing 0.5% newborn calf serum for 1 day. Cells expressing the kinase-dead PKC alpha  were generated as described previously (7). The kinase-dead PKC alpha  clone was generated by a mutation to the ATP-binding site as described previously (15).

Materials. The PKC inhibitors staurosporine, bisindolylmaleimide II, rottlerin, and Go6976 were obtained from Calbiochem. Monoclonal antibodies for PKC alpha , varepsilon , and zeta  were obtained from Transduction Laboratories; a polyclonal antibody for PKC delta  was obtained from Santa Cruz. A monoclonal antibody for ubiquitin was obtained from Zymed.

Cell lysate preparation and subcellular fractionation. Cells grew to approximately 90% confluence in 100-mm-diameter culture dishes and were then shifted to Dulbecco's modified Eagle medium containing 0.5% serum for 24 h. Cells were washed three times with ice-cold isotonic buffer (phosphate-buffered saline, containing 136 mM NaCl, 2.6 mM KCl, 1.4 mM KH2PO4, and 4.2 mM Na2HPO4, pH 7.2). For subcellular fractionation, cells from 100-mm-diameter dishes were washed and then scraped into 2 ml of homogenization buffer (20 mM Tris-HCl [pH 7.5], 5 mM NaCl, 1 mM EDTA, 5 mM MgCl2, 2 mM dithiothreitol, 200 µM phenylmethylsulfonyl fluoride, 10 µg of aprotinin per ml, 10 µg of leupeptin per ml). Cells were then disrupted with 20 strokes in a Dounce homogenizer (type B pestle), and the lysate was centrifuged at 100,000 × g for 1 h. The supernatant was collected as the cytosolic fraction. The membrane pellet was suspended in the same volume of homogenization buffer with 1% Triton X-100. After incubation for 30 min at 4°C, the suspension was centrifuged at 100,000 × g for 1 h. The supernatant was collected as the membrane fraction. For whole-cell lysates, cells were treated with 3 ml of homogenization buffer containing 1% Triton X-100 followed by centrifugation at 100,000 × g for 1 h. The supernatant was collected and used as the whole-cell lysate.

Immunoprecipitation and Western blot analysis. Extraction of proteins from cultured cells was performed as previously described (7) with a modified buffer consisting of 50 mM Tris-HCl (pH 7.5), 1% Triton X-100, 150 mM NaCl, 1 mM dithiothreitol, 0.5 mM EDTA, 0.1 mM phenylmethylsulfonyl fluoride, leupeptin (12 mg/ml), aprotinin (20 µg/ml), 100 µM sodium vanadate, 100 µM sodium pyrophosphate, 1 mM sodium fluoride, 10 mM ethylmethylmaleimide, and 50 mM hemin. Cell extracts were clarified by centrifugation at 12,000 rpm, and the supernatants (1,500 µg of protein/ml) were subjected to immunoprecipitation with anti-PKC delta , alpha , and varepsilon  antibodies. After overnight incubation at 4°C, protein A-agarose beads were added and left for an additional 3 h. Immunocomplexes were then subjected to Western blot analysis as described previously (7). Western blot analysis with antiubiquitin antibody was performed with modifications described by Avantaggiati et al. (1).

    RESULTS
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

Proteasome inhibitors block depletion of PKC isoforms. To investigate whether the ubiquitin-proteasome pathway is involved in the downregulation of PKC in response to phorbol esters, we first examined the effect of proteasome inhibitors on TPA-induced PKC depletion. MG101 and MG132, which inhibit proteasome function (11, 12), prevented the TPA-induced depletion of the alpha , delta , and varepsilon  PKC isoforms, the only TPA-responsive isoforms present in these cells (Fig. 1). E64, which shares with MG101 and MG132 the ability to inhibit calpain protease, but not the proteasome, had no effect on TPA-induced PKC depletion. We also examined the effect of these compounds on PKC zeta , a PKC isoform that is expressed in these cells but is not responsive to phorbol esters (9). As shown in Fig. 1, neither MG101 nor MG132 had any effect on PKC zeta . These data implicate the ubiquitin-proteasome pathway in the phorbol ester-induced depletion of PKC.


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  		FIG. 1.   Proteasome inhibitors prevent TPA-induced depletion of PKC. 3Y1 cells overexpressing c-Src were treated with TPA (400 nM) for the indicated times, and PKC depletion was monitored by Western blot analysis as described previously (7). The effect of MG101, MG132, or E64 (all at 50 µM) was determined by adding these compounds 30 min prior to addition of TPA as shown. The levels of PKC delta , alpha , varepsilon , and zeta  were determined by using antibodies specific for these isoforms.

PKC isoforms become ubiquitinated upon TPA treatment. The data in Fig. 1 demonstrate that compounds which inhibit proteasome function inhibit TPA-induced downregulation of PKC. Therefore, it is predicted that the affected PKC isoforms should become ubiquitinated in response to TPA. In Fig. 1, it was also observed that the anti-PKC delta  antibody recognized several higher-molecular-weight species within 30 min after TPA treatment. The appearance of these higher-molecular-weight species of PKC delta  is consistent with the rapid ubiquitination of PKC delta  in response to TPA. To investigate directly whether PKC isoforms were being ubiquitinated in response to TPA, we performed Western blot analysis of PKC isoform immunoprecipitations with antiubiquitin antibody. As shown in Fig. 2, ubiquitination of PKC alpha , delta , and varepsilon , but not PKC zeta , was detected within 30 min of TPA treatment. By 6 h, the ubiquitinated PKC isoforms were no longer detectable. However, when MG101 was used to inhibit proteasome, the ubiquitinated isoforms were still present 6 h after TPA treatment (Fig. 2). Interestingly, 24 h of treatment with MG101 alone resulted in a significant accumulation of ubiquitinated forms to a limited extent for PKC alpha  and substantially for PKC varepsilon  (Fig. 2), suggesting that ubiquitination may occur in response to physiological stimuli as well as TPA. These data demonstrate that PKC isoforms alpha , delta , and varepsilon  rapidly become ubiquitinated in response to TPA treatment and that their disappearance is blocked by inhibition of proteasome.


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  		FIG. 2.   PKC becomes ubiquitinated upon TPA treatment. The c-Src-overexpressing 3Y1 cells were treated with TPA (400 nM) for the indicated times. PKC delta , alpha , varepsilon , and zeta  were then immunoprecipitated (IP), and the level of ubiquitinated PKC was determined by Western blot analysis with an antiubiquitin antibody. The effect of MG101 (50 µM) on ubiquitination of untreated cells and cells treated with TPA is shown. Numbers on the left are molecular weights in thousands.

Degradation and ubiquitination of PKC are dependent upon PKC kinase activity. To begin to investigate the mechanism for activation of ubiquitination and proteasome degradation, we asked whether the kinase activity of PKC was important for degradation. We first investigated the effect of PKC inhibitors on the TPA-induced PKC downregulation and ubiquitination. In Fig. 3A, it is shown that the PKC inhibitors staurosporine and bisindolylmaleimide II prevented downregulation of PKC isoforms alpha , delta , and varepsilon . Interestingly, Go6976, which specifically inhibits PKC alpha  (8), prevented TPA-induced downregulation of the alpha  isoform only, and rottlerin, a more specific inhibitor of PKC delta  (4), prevented TPA-induced downregulation of the delta  isoform only. We also investigated the effect of the PKC inhibitors on the ubiquitination of PKC isoforms alpha  and delta , and as expected, the PKC inhibitors also prevented TPA-induced ubiquitination of these PKC isoforms with the same specificity observed for inhibition of downregulation (Fig. 3B). The PKC inhibitors did not inhibit translocation to the membrane of the PKC isoforms (Fig. 3C). Thus, the effects observed in Fig. 3A and B were not due to a lack of membrane association. These data indicate that TPA-induced downregulation and ubiquitination of the PKC isoforms require an active kinase activity. Consistent with a requirement for activation of PKC for downregulation, the inactive phorbol ester 4alpha -phorbol 12,13-didecanoate, which does not activate PKC (14), did not lead to the downregulation of PKC (Fig. 3D), nor did it result in the ubiquitination of PKC delta  (Fig. 3E).


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  		FIG. 3.   Degradation of PKC is dependent upon PKC kinase activity. (A) 3Y1 cells overexpressing c-Src were treated with TPA (400 nM) for 6 h to deplete the cells of PKC. This was then performed in the presence of the PKC inhibitors staurosporine (Stauro), bisindolylmaleimide II (Bis), Go6976, and rottlerin (Rott) at the indicated concentrations, and PKC levels were determined by Western blot analysis as for Fig. 1. (B) The effect of the PKC inhibitors on TPA-induced ubiquitization of PKC alpha  and delta  was determined as for Fig. 2. (C) The ability of TPA to induce translocation of the PKC isoforms from the cytosol to the membrane in the presence of PKC inhibitors was investigated by Western blot analysis of the PKC isoforms present in the cytosolic and membrane fractions before and after TPA treatment. (D and E) The effect of the inactive phorbol ester 4alpha -phorbol 12, 13-didecanoate (4alpha -PDD) (400 nM) on the induction of PKC isoform downregulation (D) and ubiquitination of PKC delta  (E) was examined as for panels A and B, respectively.

If PKC kinase activity is required for downregulation, then a kinase-dead PKC mutant should be resistant to downregulation in response to TPA. An ATP-binding site mutant of PKC alpha  (15) that was kinase dead was introduced into the c-Src-overexpressing cell line, and the ability to downregulate PKC alpha  with TPA was examined. As shown in Fig. 4A, this PKC alpha  mutant was completely resistant to downregulation by TPA. Since the kinase-dead PKC alpha  mutant could still be stimulated to associate with the membrane in response to TPA (Fig. 4B), the lack of degradation was not due to lack of membrane localization. Since PKC delta  and varepsilon  were both activated and downregulated in these cells, activation of the ubiquitin-proteasome pathway by these PKC isoforms was apparently specific for the activated isoforms only. These data further support the conclusion that activation of the kinase activity of PKC is necessary for ubiquitination and downregulation.


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  		FIG. 4.   A kinase-dead mutant of PKC alpha  is not downregulated by TPA. The c-Src-overexpressing 3Y1 cells were stably transfected with a mutant PKC alpha  gene which has a mutation in the ATP-binding site (15). (A) The mutant PKC-alpha -overexpressing cells were then treated with TPA (400 nM,) and the levels of PKC alpha , delta , and varepsilon  in these and the parental cells were determined at 6 and 72 h later as for Fig. 1. (B) The ability of TPA to induce translocation of the PKC isoforms from the cytosol to the membrane in the parental cells and in the cells expressing the kinase-dead PKC alpha  was determined as for Fig. 3C.

PKC is ubiquitinated and downregulated in response to DG in a proteasome- and kinase-dependent mechanism. Phorbol esters bind to PKC at the site that binds the physiological activator diacylglycerol (DG) (9). As shown in Fig. 2, the proteasome inhibitor MG101 stimulated an increase in the ubiquitinated PKC isoforms alpha  and varepsilon , suggesting that ubiquitination is a physiological response and not an artifact of phorbol ester treatment. We therefore wished to investigate whether ubiquitination and downregulation of PKC occur in response to DG. As shown in Fig. 5, the alpha  and delta  isoforms and to a lesser extent the varepsilon  isoform were all downregulated in response to the DG dioctoylglycerol (DiC8). This downregulation was sensitive to both proteasome and PKC inhibitors (Fig. 5A). The PKC alpha -specific Go6976 prevented downregulation of the alpha  isoform specifically. We also wished to determine whether DG stimulated ubiquitination of PKC isoforms. We added DiC8 to the 3Y1 cells and examined ubiquitination as in Fig. 2. In Fig. 5B, it is shown that DiC8 stimulated ubiquitination of PKC delta . The ubiquitination of PKC delta  was inhibited by the PKC inhibitors staurosporine, bisindolylmaleimide II, and rottlerin but not by the proteasome inhibitor MG101 or the PKC alpha  inhibitor Go6976 (Fig. 5B). These data suggest that PKC isoforms become ubiquitinated and downregulated by the physiological stimulus of DG as well as by the tumor-promoting stimulus of TPA and that downregulation is dependent upon an active kinase.


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  		FIG. 5.   PKC is downregulated and ubiquitinated in response to DG in a proteasome- and kinase-dependent mechanism. (A) c-Src-overexpressing 3Y1 cells were treated with DiC8 (10 µg/ml) for the indicated times in the presence of either E64 (50 µM), MG101 (50 µM), bisindolylmaleimide II (Bis) (1 µM), or Go6976 (2 µM), and the levels of PKC alpha , delta , and varepsilon  were then determined by Western blot analysis as for Fig. 1. (B) The effect of DiC8 on the ubiquitination of PKC delta  was determined in the presence of the proteasome inhibitor MG101 (50 µM) and the PKC inhibitors staurosporine (Stauro) (50 nM), bisindolylmaleimide II (1.0 µM), Go6976 (2.0 µM), and rottlerin (80 µM) as for Fig. 2.

TPA-induced transformation of 3Y1 cells overexpressing c-Src is blocked by proteasome inhibitors. In cells overexpressing c-Src, TPA treatment causes the appearance of transformation that is due to the depletion of PKC delta (7). We therefore investigated whether inhibitors of the ubiquitin-proteasome pathway could prevent the transformed phenotype induced by TPA in the c-Src-overexpressing cells by preventing the depletion of PKC delta . As shown in Fig. 6A, the proteasome-specific inhibitor MG101 prevented the morphological transformation of the c-Src-expressing cells induced by TPA, whereas the nonspecific protease inhibitor E64 did not prevent the morphological transformation induced by TPA. The proteasome inhibitors had no effect on the transformed phenotype induced by v-Src (Fig. 6A). The ability of MG101 to prevent the TPA-induced morphological transformation was not likely due to any effects that proteasome inhibition have upon cell cycle progression (10), since aphidicolin, which blocks cells at the G1/S boundary of the cell cycle (5), had no effect on the TPA-induced morphological transformation (data not shown). In addition, MG101 had no effect on the translocation of the PKC isoforms induced by TPA (Fig. 6B). Thus, the effect observed in Fig. 6A is not due to the inability to translocate PKC isoforms to the membrane. These data suggest that PKC delta  is downregulated by the ubiquitin-proteasome pathway and that this pathway is critical for the TPA-induced tumor promotion, as reported previously (7).


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  		FIG. 6.   TPA-induced transformation of 3Y1 cells overexpressing c-Src is blocked by proteasome inhibitors. (A) 3Y1 cells overexpressing c-Src were either untreated or treated with TPA (400 nM; 10 h) in the presence of either MG101 (50 µM) or E64 (50 µM), and the morphology of the cells was examined. The effect of MG101 on v-Src-transformed 3Y1 cells is also shown. (B) The ability of TPA to induce translocation of the PKC isoforms from the cytosol to the membrane in the presence of MG101 and E64 was investigated by Western blot analysis of the PKC isoforms present in the cytosolic and membrane fractions before and after TPA treatment.

    DISCUSSION
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

In this report, we have shown that downregulation of PKC in response to tumor-promoting phorbol esters is via the ubiqutin-proteasome pathway. In response to TPA, PKC isoforms alpha , delta , and varepsilon  all became ubiquitinated within 30 min and were degraded within 6 h in 3Y1 rat fibroblasts. Proteasome inhibitors prevented TPA-induced PKC downregulation but not ubiquitination of the PKC isoforms. Ubiquitination and downregulation of PKC isoforms were dependent on an active PKC kinase. We previously demonstrated that the downregulation of PKC delta  was responsible for the tumor-promoting effects of TPA on 3Y1 cells overexpressing c-Src (7). Consistent with PKC delta  downregulation being important for the tumor-promoting effects observed previously, the proteasome inhibitor MG101, which prevented PKC delta  downregulation in response to TPA, also prevented the TPA-induced transformation of the c-Src-overexpressing cells. Thus, the data presented here implicate the ubiquitin-proteasome pathway in phorbol ester-induced tumor promotion.

Interestingly, treatment of 3Y1 cells with MG101 induced the appearance of PKC polyubiquitinated forms, especially for PKC varepsilon , which tends to be the most constitutively activated isoform in these cells (18). This suggested that ubiquitination of PKC is a physiological response and is not unique to the response to phorbol esters. Consistent with this hypothesis, ubiquitination and downregulation were observed in response to an exogenously provided DG. DG was less potent than TPA at inducing ubiquitination and downregulation of PKC; however, this was most likely because DG can be metabolically converted to other lipids such as phosphatidic acid and monoacylglycerol.

The data presented here do not demonstrate the complete mechanism of activation of the ubiquitin-proteasome pathway; however, it is apparently regulated at the level of ubiquitination. Of special interest is the requirement for the kinase activity of the PKC isoforms. Compounds that inhibit activation of PKC prevented PKC downregulation and ubiquitination in response to TPA. Additionally, a kinase-dead PKC alpha  was completely resistant to TPA-induced downregulation. Since phorbol esters still lead to the activation and downregulation of PKC isoforms delta  and varepsilon  in cells expressing the kinase-dead PKC alpha , ubiquitination is apparently isoform specific and the activation of one PKC isoform does not stimulate ubiquitination and downregulation of other inactive PKC isoforms. Moreover, since the cells expressing the kinase-dead PKC alpha  likely still express wild-type PKC alpha , which would be activated by TPA, it is not likely that PKC alpha  activates a PKC alpha -specific ubiquitination system, because this would result in the degradation of the kinase-dead PKC alpha . Since the defect in the kinase-dead PKC alpha  mutant that was not degraded in response to TPA was in the ATP-binding site, activation of the ubiquitin-conjugating system is likely stimulated by a conformational change in PKC that involves ATP binding or hydrolysis. This suggests a suicide model for regulation of PKC where upon activation, PKC becomes ubiquitinated and thereby targeted for degradation in a negative feedback control mechanism.

    ACKNOWLEDGMENTS

We thank Robert Krauss and Neil Rosen for comments on the manuscript. We thank Shigeo Ohno for providing the PKC alpha  kinase-dead mutant. We thank Erwin Fleissner for the continued support and encouragement our lab received during his tenure as dean.

This investigation was supported by grants from the National Institutes of Health (CA46677), the Council for Tobacco Research (3075), and the American Cancer Society (BE-243) (to D.A.F.) and by a Research Centers in Minority Institutions (RCMI) award from the Division of Research Resources, National Institutes of Health (RR-03037), to Hunter College. M.P. is supported in part by NIH grant CA66229-02.

    FOOTNOTES

* Corresponding author. Mailing address: Department of Biological Sciences, Hunter College and the Graduate School of the City University of New York, 695 Park Ave., New York, NY 10021. Phone: (212) 772-4075. Fax: (212) 772-5227. E-mail: foster{at}genectr.hunter.cuny.edu.

dagger This paper is dedicated to Erwin Fleissner on the occasion of his retirement as the dean of sciences and mathematics at Hunter College.

    REFERENCES
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References

1. Avantaggiati, M. L., M. Carbone, A. Graessmann, Y. Nakatani, B. Howard, and A. S. Levine. 1996. The SV40 large T antigen and adenovirus E1a oncoproteins interact with distinct isoforms of the transcriptional co-activator, p300. EMBO J. 15:2236-2248[Medline].
2. Denning, M. F., A. A. Dlugosz, M. K. Howett, and S. H. Yuspa. 1993. Expression of an oncogenic rasHa gene in murine keratinocytes induces tyrosine phosphorylation and reduced activity of protein kinase C delta . J. Biol. Chem. 268:26079-26081[Abstract/Free Full Text].
3. Dingiovanni, J. 1992. Multistage carcinogenesis in mouse skin. Pharmacol. Ther. 54:63-128[Medline].
4. Gschwendt, M., H.-J. Muller, K. Kielbassa, R. Zang, W. Kittstein, G. Rincke, and F. Marks. 1994. Rottlerin, a novel protein kinase inhibitor. Biochem. Biophys. Res. Commun. 199:63-98[Medline].
5. Johnston, R. N., J. Feder, A. B. Hill, S. W. Sherwood, and R. T. Schimke. 1986. Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell. Mol. Cell. Biol. 6:3373-3381[Abstract/Free Full Text].
6. Lee, H. W., L. Smith, G. R. Pettit, A. Vinitsky, and J. B. Smith. 1996. Ubiquitination of protein kinase C-alpha and degradation by the proteasome. J. Biol. Chem. 271:20973-20976[Abstract/Free Full Text].
7. Lu, Z., A. Hornia, Y.-W. Jiang, Q. Zang, and D. A. Foster. 1997. Tumor-promotion by depleting cells of protein kinase C delta . Mol. Cell Biol. 17:3418-3428[Abstract].
8. Martiny-Baron, G., M. G. Kazanietz, H. Mischak, P. M. Blumberg, G. Kochs, H. Hug, D. Marme, and C. Schlachtele. 1993. Selective inhibition of protein kinase C isozymes by the indolocarbazole G0 6976. J. Biol. Chem. 268:9194-9197[Abstract/Free Full Text].
9. Nishizuka, Y. 1995. Protein kinases 5: protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 9:484-496[Abstract].
10. Pagano, M., S. W. Tam, A. M. Theodoras, P. Beer-Romero, G. Del Sal, V. Chau, P. R. Yew, G. F. Draetta, and M. Rolfe. 1995. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269:682-685[Abstract/Free Full Text].
11. Palombella, V., O. Rando, A. Goldberg, and T. Maniatis. 1994. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and activation of NF-kappa B. Cell 78:773-785[Medline].
12. Rock, K. L., C. Gramm, L. Rothstein, K. Clark, R. Stein, L. Dick, D. Hwang, and A. L. Goldberg. 1994. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761-771[Medline].
13. Rolfe, M., M. I. Chiu, and M. Pagano. 1997. The ubiquitin-mediated proteolitic pathway as a therapeutic area. J. Mol. Med. 75:5-17[Medline].
14. Suzuki, A., O. Kozawa, and K. Kato. 1996. Protein kinase C activation inhibits stress-induced synthesis of heat shock protein 27 in osteoblast-like cells: function of arachidonic acid. J. Cell. Biochem. 62:69-75[Medline].
15. Ueda, Y., S. Hirai, S. Osada, A. Suzuku, K. Mizuno, and S. Ohno. 1996. Protein kinase C delta  activates the MEK-ERK pathway in a manner independent of Ras and dependent on Raf. J. Biol. Chem. 271:23512-23519[Abstract/Free Full Text].
16. Young, S., P. J. Parker, A. Ulrich, and S. Stabel. 1987. Down-regulation of protein kinase C is due to an increased rate of degradation. Biochem. J. 244:711-717[Medline].
17. Yupsa, S. H., and M. C. Poirier. 1988. Chemical carcinogenesis: from animal models to molecular models in one decade. Adv. Cancer. Res. 50:25-70[Medline].
18. Zang, Q., P. Frankel, and D. A. Foster. 1995. Selective activation of protein kinase C isoforms by v-Src. Cell Growth Differ. 6:1367-1373[Abstract].
19. Zang, Q., Z. Lu, M. Curto, N. Barile, D. Shalloway, and D. A. Foster. 1997. Interaction between v-Src and protein kinase C delta  in v-Src-transformed fibroblasts. J. Biol. Chem. 272:13275-13280[Abstract/Free Full Text].

Mol Cell Biol, February 1998, p. 839-845, Vol. 18, No. 2
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Copyright © 1998, American Society for Microbiology. All rights reserved.


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  • Kim, H. S., Lim, I. K. (2009). Phosphorylated Extracellular Signal-regulated Protein Kinases 1 and 2 Phosphorylate Sp1 on Serine 59 and Regulate Cellular Senescence via Transcription of p21Sdi1/Cip1/Waf1. J. Biol. Chem. 284: 15475-15486 [Abstract] [Full Text]  
  • Adjobo-Hermans, M. J. W., Goedhart, J., Gadella, T. W. J. Jr (2008). Regulation of PLC{beta}1a membrane anchoring by its substrate phosphatidylinositol (4,5)-bisphosphate. J. Cell Sci. 121: 3770-3777 [Abstract] [Full Text]  
  • Wang, Y., Zhu, M., Ayalew, M., Ruff, J. A. (2008). Down-regulation of Pkc1-mediated Signaling by the Deubiquitinating Enzyme Ubp3. J. Biol. Chem. 283: 1954-1961 [Abstract] [Full Text]  
  • Chen, D., Gould, C., Garza, R., Gao, T., Hampton, R. Y., Newton, A. C. (2007). Amplitude Control of Protein Kinase C by RINCK, a Novel E3 Ubiquitin Ligase. J. Biol. Chem. 282: 33776-33787 [Abstract] [Full Text]  
  • Fang, D., Hawke, D., Zheng, Y., Xia, Y., Meisenhelder, J., Nika, H., Mills, G. B., Kobayashi, R., Hunter, T., Lu, Z. (2007). Phosphorylation of beta-Catenin by AKT Promotes beta-Catenin Transcriptional Activity. J. Biol. Chem. 282: 11221-11229 [Abstract] [Full Text]  
  • Vallentin, A., Mochly-Rosen, D. (2007). RBCK1, a Protein Kinase CbetaI (PKCbetaI)-interacting Protein, Regulates PKCbeta-dependent Function. J. Biol. Chem. 282: 1650-1657 [Abstract] [Full Text]  
  • Xia, Y., Wang, J., Xu, S., Johnson, G. L., Hunter, T., Lu, Z. (2007). MEKK1 Mediates the Ubiquitination and Degradation of c-Jun in Response to Osmotic Stress. Mol. Cell. Biol. 27: 510-517 [Abstract] [Full Text]  
  • Lee, O.-H., Xu, J., Fueyo, J., Fuller, G. N., Aldape, K. D., Alonso, M. M., Piao, Y., Liu, T.-J., Lang, F. F., Bekele, B. N., Gomez-Manzano, C. (2006). Expression of the Receptor Tyrosine Kinase Tie2 in Neoplastic Glial Cells Is Associated with Integrin {beta}1-Dependent Adhesion to the Extracellular Matrix. Mol Cancer Res 4: 915-926 [Abstract] [Full Text]  
  • Buganim, Y., Kalo, E., Brosh, R., Besserglick, H., Nachmany, I., Rais, Y., Stambolsky, P., Tang, X., Milyavsky, M., Shats, I., Kalis, M., Goldfinger, N., Rotter, V. (2006). Mutant p53 Protects Cells from 12-O-Tetradecanoylphorbol-13-Acetate-Induced Death by Attenuating Activating Transcription Factor 3 Induction.. Cancer Res. 66: 10750-10759 [Abstract] [Full Text]  
  • Gao, T., Newton, A. C. (2006). Invariant Leu Preceding Turn Motif Phosphorylation Site Controls the Interaction of Protein Kinase C with Hsp70. J. Biol. Chem. 281: 32461-32468 [Abstract] [Full Text]  
  • Cozzi, S.-J., Parsons, P. G., Ogbourne, S. M., Pedley, J., Boyle, G. M. (2006). Induction of Senescence in Diterpene Ester-Treated Melanoma Cells via Protein Kinase C-Dependent Hyperactivation of the Mitogen-Activated Protein Kinase Pathway.. Cancer Res. 66: 10083-10091 [Abstract] [Full Text]  
  • Powell, S. R. (2006). The Cardiac 26S Proteasome: Regulating the Regulator. Circ. Res. 99: 342-345 [Full Text]  
  • Choi, S. H., Hyman, T., Blumberg, P. M. (2006). Differential Effect of Bryostatin 1 and Phorbol 12-Myristate 13-Acetate on HOP-92 Cell Proliferation Is Mediated by Down-regulation of Protein Kinase C{delta}.. Cancer Res. 66: 7261-7269 [Abstract] [Full Text]  
  • Aaltonen, V., Koivunen, J., Laato, M., Peltonen, J. (2006). Heterogeneity of Cellular Proliferation within Transitional Cell Carcinoma: Correlation of Protein Kinase C Alpha/betaI Expression and Activity. J. Histochem. Cytochem. 54: 795-806 [Abstract] [Full Text]  
  • Feng, H., Ren, M., Rubin, C. S. (2006). Conserved Domains Subserve Novel Mechanisms and Functions in DKF-1, a Caenorhabditis elegans Protein Kinase D. J. Biol. Chem. 281: 17815-17826 [Abstract] [Full Text]  
  • Lopez-Avalos, M. D., Duvivier-Kali, V. F., Xu, G., Bonner-Weir, S., Sharma, A., Weir, G. C. (2006). Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets.. Diabetes 55: 1223-1231 [Abstract] [Full Text]  
  • Inagaki, K., Churchill, E., Mochly-Rosen, D. (2006). Epsilon protein kinase C as a potential therapeutic target for the ischemic heart. Cardiovasc Res 70: 222-230 [Abstract] [Full Text]  
  • Yogosawa, S., Hatakeyama, S., Nakayama, K. I., Miyoshi, H., Kohsaka, S., Akazawa, C. (2005). Ubiquitylation and Degradation of Serum-inducible Kinase by hVPS18, a RING-H2 Type Ubiquitin Ligase. J. Biol. Chem. 280: 41619-41627 [Abstract] [Full Text]  
  • Springett, G. M., Bonham, L., Hummer, A., Linkov, I., Misra, D., Ma, C., Pezzoni, G., Di Giovine, S., Singer, J., Kawasaki, H., Spriggs, D., Soslow, R., Dupont, J. (2005). Lysophosphatidic Acid Acyltransferase-{beta} Is a Prognostic Marker and Therapeutic Target in Gynecologic Malignancies. Cancer Res. 65: 9415-9425 [Abstract] [Full Text]  
  • Pines, A., Perrone, L., Bivi, N., Romanello, M., Damante, G., Gulisano, M., Kelley, M. R., Quadrifoglio, F., Tell, G. (2005). Activation of APE1/Ref-1 is dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP. Nucleic Acids Res 33: 4379-4394 [Abstract] [Full Text]  
  • Das, S., Powell, S. R., Wang, P., Divald, A., Nesaretnam, K., Tosaki, A., Cordis, G. A., Maulik, N., Das, D. K. (2005). Cardioprotection with palm tocotrienol: antioxidant activity of tocotrienol is linked with its ability to stabilize proteasomes. Am. J. Physiol. Heart Circ. Physiol. 289: H361-H367 [Abstract] [Full Text]  
  • Kim, D. J., Murray, I. A., Burns, A. M., Gonzalez, F. J., Perdew, G. H., Peters, J. M. (2005). Peroxisome Proliferator-activated Receptor-{beta}/{delta} Inhibits Epidermal Cell Proliferation by Down-regulation of Kinase Activity. J. Biol. Chem. 280: 9519-9527 [Abstract] [Full Text]  
  • San-Juan-Vergara, H., Peeples, M. E., Lockey, R. F., Mohapatra, S. S. (2004). Protein Kinase C-{alpha} Activity Is Required for Respiratory Syncytial Virus Fusion to Human Bronchial Epithelial Cells. J. Virol. 78: 13717-13726 [Abstract] [Full Text]  
  • Wojcik, C., Di Napoli, M. (2004). Ubiquitin-Proteasome System and Proteasome Inhibition: New Strategies in Stroke Therapy. Stroke 35: 1506-1518 [Abstract] [Full Text]  
  • Kim, D. J., Akiyama, T. E., Harman, F. S., Burns, A. M., Shan, W., Ward, J. M., Kennett, M. J., Gonzalez, F. J., Peters, J. M. (2004). Peroxisome Proliferator-activated Receptor {beta} ({delta})-dependent Regulation of Ubiquitin C Expression Contributes to Attenuation of Skin Carcinogenesis. J. Biol. Chem. 279: 23719-23727 [Abstract] [Full Text]  
  • Osmanagic-Myers, S., Wiche, G. (2004). Plectin-RACK1 (Receptor for Activated C Kinase 1) Scaffolding: A NOVEL MECHANISM TO REGULATE PROTEIN KINASE C ACTIVITY. J. Biol. Chem. 279: 18701-18710 [Abstract] [Full Text]  
  • JACKSON, D. N., FOSTER, D. A. (2004). The enigmatic protein kinase C{delta}: complex roles in cell proliferation and survival. FASEB J. 18: 627-636 [Abstract] [Full Text]  
  • Abbas, T., White, D., Hui, L., Yoshida, K., Foster, D. A., Bargonetti, J. (2004). Inhibition of Human p53 Basal Transcription by Down-regulation of Protein Kinase C{delta}. J. Biol. Chem. 279: 9970-9977 [Abstract] [Full Text]  
  • Leontieva, O. V., Black, J. D. (2004). Identification of Two Distinct Pathways of Protein Kinase C{alpha} Down-regulation in Intestinal Epithelial Cells. J. Biol. Chem. 279: 5788-5801 [Abstract] [Full Text]  
  • Leithe, E., Cruciani, V., Sanner, T., Mikalsen, S.-O., Rivedal, E. (2003). Recovery of gap junctional intercellular communication after phorbol ester treatment requires proteasomal degradation of protein kinase C. Carcinogenesis 24: 1239-1245 [Abstract] [Full Text]  
  • Gardner, A. M., Olah, M. E. (2003). Distinct Protein Kinase C Isoforms Mediate Regulation of Vascular Endothelial Growth Factor Expression by A2A Adenosine Receptor Activation and Phorbol Esters in Pheochromocytoma PC12 Cells. J. Biol. Chem. 278: 15421-15428 [Abstract] [Full Text]  
  • Keshamouni, V. G., Mattingly, R. R., Reddy, K. B. (2002). Mechanism of 17-beta -Estradiol-induced Erk1/2 Activation in Breast Cancer Cells. A ROLE FOR HER2 AND PKC-delta. J. Biol. Chem. 277: 22558-22565 [Abstract] [Full Text]  
  • Junoy, B., Maccario, H., Mas, J.-L., Enjalbert, A., Drouva, S. V. (2002). Proteasome Implication in Phorbol Ester- and GnRH-Induced Selective Down-Regulation of PKC ({alpha}, {epsilon}, {zeta}) in {alpha}T3-1 and L{beta}T2 Gonadotrope Cell Lines. Endocrinology 143: 1386-1403 [Abstract] [Full Text]  
  • Floyd, Z. E., Stephens, J. M. (2002). Interferon-gamma -mediated Activation and Ubiquitin-Proteasome-dependent Degradation of PPARgamma in Adipocytes. J. Biol. Chem. 277: 4062-4068 [Abstract] [Full Text]  
  • Peng, Z., Grimberg, E., Sagi-Eisenberg, R. (2002). Suppression of Synaptotagmin II restrains phorbolester-induced downregulation of protein kinase C{alpha} by diverting the kinase from a degradative pathway to the recycling endocytic compartment. J. Cell Sci. 115: 3083-3092 [Abstract] [Full Text]  
  • Benimetskaya, L., Miller, P., Benimetsky, S., Maciaszek, A., Guga, P., Beaucage, S. L., Wilk, A., Grajkowski, A., Halperin, A. L., Stein, C. A. (2001). Inhibition of Potentially Anti-Apoptotic Proteins by Antisense Protein Kinase C-alpha (Isis 3521) and Antisense bcl-2 (G3139) Phosphorothioate Oligodeoxynucleotides: Relationship to the Decreased Viability of T24 Bladder and PC3 Prostate Cancer Cells. Mol. Pharmacol. 60: 1296-1307 [Abstract] [Full Text]  
  • Okuda, H., Saitoh, K., Hirai, S.-i., Iwai, K., Takaki, Y., Baba, M., Minato, N., Ohno, S., Shuin, T. (2001). The von Hippel-Lindau Tumor Suppressor Protein Mediates Ubiquitination of Activated Atypical Protein Kinase C. J. Biol. Chem. 276: 43611-43617 [Abstract] [Full Text]  
  • Hsieh, M. M., Hegde, V., Kelley, M. R., Deutsch, W. A. (2001). Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and PKC phosphorylation. Nucleic Acids Res 29: 3116-3122 [Abstract] [Full Text]  
  • de Hoog, C. L., Koehler, J. A., Goldstein, M. D., Taylor, P., Figeys, D., Moran, M. F. (2001). Ras Binding Triggers Ubiquitination of the Ras Exchange Factor Ras-GRF2. Mol. Cell. Biol. 21: 2107-2117 [Abstract] [Full Text]  
  • Chen, D., Fong, H. W., Davis, J. S. (2001). Induction of c-fos and c-junMessenger Ribonucleic Acid Expression by Prostaglandin F2{{alpha}} Is Mediated by a Protein Kinase C-Dependent Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Bovine Luteal Cells. Endocrinology 142: 887-895 [Abstract] [Full Text]  
  • Roche, J. K., Martins, C. A. P., Cosme, R., Fayer, R., Guerrant, R. L. (2000). Transforming Growth Factor beta 1 Ameliorates Intestinal Epithelial Barrier Disruption by Cryptosporidium parvum In Vitro in the Absence of Mucosal T Lymphocytes. Infect. Immun. 68: 5635-5644 [Abstract] [Full Text]  
  • Lu, Z., Hornia, A., Joseph, T., Sukezane, T., Frankel, P., Zhong, M., Bychenok, S., Xu, L., Feig, L. A., Foster, D. A. (2000). Phospholipase D and RalA Cooperate with the Epidermal Growth Factor Receptor To Transform 3Y1 Rat Fibroblasts. Mol. Cell. Biol. 20: 462-467 [Abstract] [Full Text]  
  • Prevostel, C, Alice, V, Joubert, D, Parker, P. (2000). Protein kinase C(alpha) actively downregulates through caveolae-dependent traffic to an endosomal compartment. J. Cell Sci. 113: 2575-2584 [Abstract]  
  • Lorenzo, P. S., Bogi, K., Hughes, K. M., Beheshti, M., Bhattacharyya, D., Garfield, S. H., Pettit, G. R., Blumberg, P. M. (1999). Differential Roles of the Tandem C1 Domains of Protein Kinase C {{delta}} in the Biphasic Down-Regulation Induced by Bryostatin 1. Cancer Res. 59: 6137-6144 [Abstract] [Full Text]  
  • Hornia, A., Lu, Z., Sukezane, T., Zhong, M., Joseph, T., Frankel, P., Foster, D. A. (1999). Antagonistic Effects of Protein Kinase C alpha and delta on Both Transformation and Phospholipase D Activity Mediated by the Epidermal Growth Factor Receptor. Mol. Cell. Biol. 19: 7672-7680 [Abstract] [Full Text]  
  • Wilkinson, K. D. (1999). Ubiquitin-Dependent Signaling: The Role of Ubiquitination in the Response of Cells to Their Environment.. J. Nutr. 129: 1933-1936 [Abstract] [Full Text]  
  • Nakhost, A., Dyer, J. R., Pepio, A. M., Fan, X., Sossin, W. S. (1999). Protein Kinase C Phosphorylated at a Conserved Threonine Is Retained in the Cytoplasm. J. Biol. Chem. 274: 28944-28949 [Abstract] [Full Text]  
  • Strassheim, D., May, L. G., Varker, K. A., Puhl, H. L., Phelps, S. H., Porter, R. A., Aronstam, R. S., Noti, J. D., Williams, C. L. (1999). M3 Muscarinic Acetylcholine Receptors Regulate Cytoplasmic Myosin by a Process Involving RhoA and Requiring Conventional Protein Kinase C Isoforms. J. Biol. Chem. 274: 18675-18685 [Abstract] [Full Text]  
  • Corbit, K. C., Foster, D. A., Rosner, M. R. (1999). Protein Kinase Cdelta Mediates Neurogenic but Not Mitogenic Activation of Mitogen-Activated Protein Kinase in Neuronal Cells. Mol. Cell. Biol. 19: 4209-4218 [Abstract] [Full Text]  
  • Li, H.-L., Davis, W., Pure, E. (1999). Suboptimal Cross-linking of Antigen Receptor Induces Syk-dependent Activation of p70S6 Kinase through Protein Kinase C and Phosphoinositol 3-Kinase. J. Biol. Chem. 274: 9812-9820 [Abstract] [Full Text]  
  • Blake, R. A., Garcia-Paramio, P., Parker, P. J., Courtneidge, S. A. (1999). Src Promotes PKC{{delta}} Degradation. Cell Growth Differ. 10: 231-241 [Abstract] [Full Text]  
  • Stempka, L., Schnolzer, M., Radke, S., Rincke, G., Marks, F., Gschwendt, M. (1999). Requirements of Protein Kinase Cdelta for Catalytic Function. ROLE OF GLUTAMIC ACID 500 AND AUTOPHOSPHORYLATION ON SERINE 643. J. Biol. Chem. 274: 8886-8892 [Abstract] [Full Text]  
  • Spitaler, M., Villunger, A., Grunicke, H., Uberall, F. (2000). Unique Structural and Functional Properties of the ATP-binding Domain of Atypical Protein Kinase C-iota. J. Biol. Chem. 275: 33289-33296 [Abstract] [Full Text]  
  • Frasch, S. C., Henson, P. M., Kailey, J. M., Richter, D. A., Janes, M. S., Fadok, V. A., Bratton, D. L. (2000). Regulation of Phospholipid Scramblase Activity during Apoptosis and Cell Activation by Protein Kinase Cdelta. J. Biol. Chem. 275: 23065-23073 [Abstract] [Full Text]  
  • Xu, A., Wang, Y., Xu, L. Y., Gilmour, R. S. (2001). Protein Kinase C alpha -mediated Negative Feedback Regulation Is Responsible for the Termination of Insulin-like Growth Factor I-induced Activation of Nuclear Phospholipase C beta 1 in Swiss 3T3 Cells. J. Biol. Chem. 276: 14980-14986 [Abstract] [Full Text]  
  • Smith, L., Chen, L., Reyland, M. E., DeVries, T. A., Talanian, R. V., Omura, S., Smith, J. B. (2000). Activation of Atypical Protein Kinase C zeta by Caspase Processing and Degradation by the Ubiquitin-Proteasome System. J. Biol. Chem. 275: 40620-40627 [Abstract] [Full Text]  

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