This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, W Articles by Pierce, J H Search for Related Content PubMed PubMed Citation Articles by Li, W Articles by Pierce, J H

Stimulation of the platelet-derived growth factor beta receptor signaling pathway activates protein kinase C-delta.

Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.

ABSTRACT

The murine myeloid progenitor cell line 32D was recently shown to undergo monocytic differentiation when protein kinase C-delta (PKC-delta) was overexpressed and activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) (H. Mischak, J.H. Pierce, J. Goodnight, M.G. Kazanietz, P.M. Blumberg, and J.F. Mushinski, J. Biol. Chem. 268:20110-20115, 1993). Tyrosine phosphorylation of PKC-delta occurred when PKC-delta-transfected 32D cells were stimulated by TPA (W. Li, H. Mischak, J.-C. Yu, L.-M. Wang, J.F. Mushinski, M.A. Heidaran, and J.H. Pierce, J. Biol. Chem. 269:2349-2352, 1994). In order to elucidate the role played by PKC-delta in response to activation of a receptor tyrosine kinase, we transfected platelet-derived growth factor beta receptor (PDGF-beta R) alone (32D/PDGF-beta R) or together with PKC-delta (32D/PDGF-beta R/PKC-delta) into 32D cells. NIH 3T3 cells which endogenously express both PDGF-alpha R and PDGF-beta R were also transfected with PKC-delta (NIH 3T3/PKC-delta). Like TPA treatment, PDGF-BB stimulation caused striking phosphorylation of PKC-delta in vivo and translocation of some PKC-delta from the cytosol fraction to the membrane fraction in both cell systems. Some of the phosphorylation induced by PDGF-BB treatment was found to be on a tyrosine residue(s). Tyrosine-phosphorylated PKC-delta was observed only for the membrane fraction after stimulation with PDGF-BB or TPA. The enzymatic activity of PKC-delta in the membrane fraction also increased after stimulation with TPA or PDGF, providing a positive correlation between PKC-delta tyrosine phosphorylation and its activation. Overnight treatment of 32D/PDGF-beta R/PKC-delta cells with PDGF-BB induced monocytic differentiation as judged by an increase in expression of cell surface macrophage differentiation markers. PDGF-BB had much weaker effects on 32D/PDGF-beta R cell differentiation, suggesting that increased PKC-delta expression enhanced monocytic differentiation. These results indicate that PKC-delta is a downstream molecule in the PDGFR signaling pathway and may play a pivotal role in PDGF-beta R-mediated cell differentiation.

This article has been cited by other articles:

• Uekita, T., Jia, L., Narisawa-Saito, M., Yokota, J., Kiyono, T., Sakai, R. (2007). CUB Domain-Containing Protein 1 Is a Novel Regulator of Anoikis Resistance in Lung Adenocarcinoma. Mol. Cell. Biol. 27: 7649-7660 [Abstract] [Full Text]  
• Choi, B.-H., Hur, E.-M., Lee, J.-H., Jun, D.-J., Kim, K.-T. (2006). Protein kinase C{delta}-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death. J. Cell Sci. 119: 1329-1340 [Abstract] [Full Text]  
• Choi, S.-Y., Kim, M.-J., Kang, C.-M., Bae, S., Cho, C.-K., Soh, J.-W., Kim, J.-H., Kang, S., Chung, H. Y., Lee, Y.-S., Lee, S.-J. (2006). Activation of Bak and Bax through c-Abl-Protein Kinase C{delta}-p38 MAPK Signaling in Response to Ionizing Radiation in Human Non-small Cell Lung Cancer Cells. J. Biol. Chem. 281: 7049-7059 [Abstract] [Full Text]  
• Murugappan, S., Shankar, H., Bhamidipati, S., Dorsam, R. T., Jin, J., Kunapuli, S. P. (2005). Molecular mechanism and functional implications of thrombin-mediated tyrosine phosphorylation of PKC{delta} in platelets. Blood 106: 550-557 [Abstract] [Full Text]  
• Pula, G., Crosby, D., Baker, J., Poole, A. W. (2005). Functional Interaction of Protein Kinase C{alpha} with the Tyrosine Kinases Syk and Src in Human Platelets. J. Biol. Chem. 280: 7194-7205 [Abstract] [Full Text]  
• Romanova, L. Y., Hashimoto, S., Chay, K.-O., Blagosklonny, M. V., Sabe, H., Mushinski, J. F. (2004). Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive. J. Cell Sci. 117: 3759-3768 [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]  
• Tapia, J. A., Garcia-Marin, L. J., Jensen, R. T. (2003). Cholecystokinin-stimulated Protein Kinase C-{delta} Kinase Activation, Tyrosine Phosphorylation, and Translocation Are Mediated by Src Tyrosine Kinases in Pancreatic Acinar Cells. J. Biol. Chem. 278: 35220-35230 [Abstract] [Full Text]  
• Crosby, D., Poole, A. W. (2003). Physical and Functional Interaction between Protein Kinase C {delta} and Fyn Tyrosine Kinase in Human Platelets. J. Biol. Chem. 278: 24533-24541 [Abstract] [Full Text]  
• Clark, A. S., West, K. A., Blumberg, P. M., Dennis, P. A. (2003). Altered Protein Kinase C (PKC) Isoforms in Non-Small Cell Lung Cancer Cells: PKC{delta} Promotes Cellular Survival and Chemotherapeutic Resistance. Cancer Res. 63: 780-786 [Abstract] [Full Text]  
• Junttila, I., Bourette, R. P., Rohrschneider, L. R., Silvennoinen, O. (2003). M-CSF induced differentiation of myeloid precursor cells involves activation of PKC-{delta} and expression of Pkare. J. Leukoc. Biol. 73: 281-288 [Abstract] [Full Text]  
• Yoshida, K., Miki, Y., Kufe, D. (2002). Activation of SAPK/JNK Signaling by Protein Kinase Cdelta in Response to DNA Damage. J. Biol. Chem. 277: 48372-48378 [Abstract] [Full Text]  
• Page, K., Li, J., Corbit, K. C., Rumilla, K. M., Soh, J.-W., Weinstein, I. B., Albanese, C., Pestell, R. G., Rosner, M. R., Hershenson, M. B. (2002). Regulation of Airway Smooth Muscle Cyclin D1 Transcription by Protein Kinase C-{delta}. Am. J. Respir. Cell Mol. Bio. 27: 204-213 [Abstract] [Full Text]  
• Ren, J., Li, Y., Kufe, D. (2002). Protein Kinase C delta Regulates Function of the DF3/MUC1 Carcinoma Antigen in beta -Catenin Signaling. J. Biol. Chem. 277: 17616-17622 [Abstract] [Full Text]  
• Joseloff, E., Cataisson, C., Aamodt, H., Ocheni, H., Blumberg, P., Kraker, A. J., Yuspa, S. H. (2002). Src Family Kinases Phosphorylate Protein Kinase C delta on Tyrosine Residues and Modify the Neoplastic Phenotype of Skin Keratinocytes. J. Biol. Chem. 277: 12318-12323 [Abstract] [Full Text]  
• Wakino, S., Kintscher, U., Liu, Z., Kim, S., Yin, F., Ohba, M., Kuroki, T., Schonthal, A. H., Hsueh, W. A., Law, R. E. (2001). Peroxisome Proliferator-activated Receptor gamma Ligands Inhibit Mitogenic Induction of p21Cip1 by Modulating the Protein Kinase Cdelta Pathway in Vascular Smooth Muscle Cells. J. Biol. Chem. 276: 47650-47657 [Abstract] [Full Text]  
• Benes, C., Soltoff, S. P. (2001). Modulation of PKC{delta} tyrosine phosphorylation and activity in salivary and PC-12 cells by Src kinases. Am. J. Physiol. Cell Physiol. 280: C1498-C1510 [Abstract] [Full Text]  
• Konishi, H., Yamauchi, E., Taniguchi, H., Yamamoto, T., Matsuzaki, H., Takemura, Y., Ohmae, K., Kikkawa, U., Nishizuka, Y. (2001). Phosphorylation sites of protein kinase C delta in H2O2-treated cells and its activation by tyrosine kinase invitro. Proc. Natl. Acad. Sci. USA 10.1073/pnas.111158798v1 [Abstract] [Full Text]  
• Kajimoto, T., Ohmori, S., Shirai, Y., Sakai, N., Saito, N. (2001). Subtype-Specific Translocation of the {delta} Subtype of Protein Kinase C and Its Activation by Tyrosine Phosphorylation Induced by Ceramide in HeLa Cells. Mol. Cell. Biol. 21: 1769-1783 [Abstract] [Full Text]  
• Acs, P., Beheshti, M., Szallasi, Z., Li, L., Yuspa, S. H., Blumberg, P. M. (2000). Effect of a tyrosine 155 to phenylalanine mutation of protein kinase C{delta} on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts. Carcinogenesis 21: 887-891 [Abstract] [Full Text]  
• Kovanen, P. E., Junttila, I., Takaluoma, K., Saharinen, P., Valmu, L., Li, W., Silvennoinen, O. (2000). Regulation of Jak2 tyrosine kinase by protein kinase C during macrophage differentiation of IL-3-dependent myeloid progenitor cells. Blood 95: 1626-1632 [Abstract] [Full Text]  
• Liu, Y., Witte, S., Liu, Y.-C., Doyle, M., Elly, C., Altman, A. (2000). Regulation of Protein Kinase Ctheta Function during T Cell Activation by Lck-mediated Tyrosine Phosphorylation. J. Biol. Chem. 275: 3603-3609 [Abstract] [Full Text]  
• Efimova, T., Eckert, R. L. (2000). Regulation of Human Involucrin Promoter Activity by Novel Protein Kinase C Isoforms. J. Biol. Chem. 275: 1601-1607 [Abstract] [Full Text]  
• Braiman, L., Alt, A., Kuroki, T., Ohba, M., Bak, A., Tennenbaum, T., Sampson, S. R. (1999). Protein Kinase C{delta} Mediates Insulin-Induced Glucose Transport in Primary Cultures of Rat Skeletal Muscle. Mol. Endocrinol. 13: 2002-2012 [Abstract] [Full Text]  
• Kiley, S. C., Clark, K. J., Goodnough, M., Welch, D. R., Jaken, S. (1999). Protein Kinase C {{delta}} Involvement in Mammary Tumor Cell Metastasis. Cancer Res. 59: 3230-3238 [Abstract] [Full Text]  
• Soon, L., Flechner, L., Gutkind, J. S., Wang, L.-H., Baserga, R., Pierce, J. H., Li, W. (1999). Insulin-Like Growth Factor I Synergizes with Interleukin 4 for Hematopoietic Cell Proliferation Independent of Insulin Receptor Substrate Expression. Mol. Cell. Biol. 19: 3816-3828 [Abstract] [Full Text]  
• Miranti, C. K., Ohno, S., Brugge, J. S. (1999). Protein Kinase C Regulates Integrin-induced Activation of the Extracellular Regulated Kinase Pathway Upstream of Shc. J. Biol. Chem. 274: 10571-10581 [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]  
• Brodie, C., Bogi, K., Acs, P., Lorenzo, P. S., Baskin, L., Blumberg, P. M. (1998). Protein Kinase C delta  (PKCdelta ) Inhibits the Expression of Glutamine Synthetase in Glial Cells via the PKCdelta Regulatory Domain and Its Tyrosine Phosphorylation. J. Biol. Chem. 273: 30713-30718 [Abstract] [Full Text]  
• Li, W., Jiang, Y.-X., Zhang, J., Soon, L., Flechner, L., Kapoor, V., Pierce, J. H., Wang, L.-H. (1998). Protein Kinase C-delta Is an Important Signaling Molecule in Insulin-Like Growth Factor I Receptor-Mediated Cell Transformation. Mol. Cell. Biol. 18: 5888-5898 [Abstract] [Full Text]  
• Ohmori, S., Shirai, Y., Sakai, N., Fujii, M., Konishi, H., Kikkawa, U., Saito, N. (1998). Three Distinct Mechanisms for Translocation and Activation of the delta  Subspecies of Protein Kinase C. Mol. Cell. Biol. 18: 5263-5271 [Abstract] [Full Text]  
• Rui, L., Carter-Su, C. (1998). Platelet-derived Growth Factor (PDGF) Stimulates the Association of SH2-Bbeta with PDGF Receptor and Phosphorylation of SH2-Bbeta. J. Biol. Chem. 273: 21239-21245 [Abstract] [Full Text]  
• Vecchi, M., Rudolph-Owen, L. A., Brown, C. L., Dempsey, P. J., Carpenter, G. (1998). Tyrosine Phosphorylation and Proteolysis. PERVANADATE-INDUCED, METALLOPROTEASE-DEPENDENT CLEAVAGE OF THE ErbB-4 RECEPTOR AND AMPHIREGULIN. J. Biol. Chem. 273: 20589-20595 [Abstract] [Full Text]  
• Maloney, J. A., Tsygankova, O., Szot, A., Yang, L., Li, Q., Williamson, J. R. (1998). Differential translocation of protein kinase C isozymes by phorbol esters, EGF, and ANG II in rat liver WB cells. Am. J. Physiol. Cell Physiol. 274: C974-C982 [Abstract] [Full Text]  
• Soltoff, S. P., Avraham, H., Avraham, S., Cantley, L. C. (1998). Activation of P2Y2 Receptors by UTP and ATP Stimulates Mitogen-activated Kinase Activity through a Pathway That Involves Related Adhesion Focal Tyrosine Kinase and Protein Kinase C. J. Biol. Chem. 273: 2653-2660 [Abstract] [Full Text]  
• Acs, P., Wang, Q. J., Bogi, K., Marquez, A. M., Lorenzo, P. S., Biro, T., Szallasi, Z., Mushinski, J. F., Blumberg, P. M. (1997). Both the Catalytic and Regulatory Domains of Protein Kinase C Chimeras Modulate the Proliferative Properties of NIH 3T3 Cells. J. Biol. Chem. 272: 28793-28799 [Abstract] [Full Text]  
• Li, W., Zhang, J., Bottaro, D. P., Li, W., Pierce, J. H. (1997). Identification of Serine 643 of Protein Kinase C-delta as an Important Autophosphorylation Site for Its Enzymatic Activity. J. Biol. Chem. 272: 24550-24555 [Abstract] [Full Text]  
• Li, W., Li, W., Chen, X.-H., Kelley, C. A., Alimandi, M., Zhang, J., Chen, Q., Bottaro, D. P., Pierce, J. H. (1996). Identification of Tyrosine 187as a Protein Kinase C-delta Phosphorylation Site. J. Biol. Chem. 271: 26404-26409 [Abstract] [Full Text]  
• Uren, A., Yu, J.-C., Li, W., Chung, I.-Y., Mahadevan, D., Pierce, J. H., Heidaran, M. A. (1996). Identification of a Domain within the Carboxyl-terminal Region of the beta Platelet-derived Growth Factor (PDGF) Receptor That Mediates the High Transforming Activity of PDGF. J. Biol. Chem. 271: 11051-11054 [Abstract] [Full Text]  
• Denning, M. F., Dlugosz, A. A., Threadgill, D. W., Magnuson, T., Yuspa, S. H. (1996). Activation of the Epidermal Growth Factor Receptor Signal Transduction Pathway Stimulates Tyrosine Phosphorylation of Protein Kinase C [IMAGE]. J. Biol. Chem. 271: 5325-5331 [Abstract] [Full Text]  
• Soltoff, S. P., Toker, A. (1995). Carbachol, Substance P, and Phorbol Ester Promote the Tyrosine Phosphorylation of Protein Kinase C[IMAGE] in Salivary Gland Epithelial Cells. J. Biol. Chem. 270: 13490-13495 [Abstract] [Full Text]  
• Li, W., Yu, J.-C., Shin, D.-Y., Pierce, J. H. (1995). Characterization of a Protein Kinase C-[IMAGE] (PKC-[IMAGE]) ATP Binding Mutant. J. Biol. Chem. 270: 8311-8318 [Abstract] [Full Text]  
• Bahr, C., Rohwer, A., Stempka, L., Rincke, G., Marks, F., Gschwendt, M. (2000). DIK, a Novel Protein Kinase That Interacts with Protein Kinase Cdelta . CLONING, CHARACTERIZATION, AND GENE ANALYSIS. J. Biol. Chem. 275: 36350-36357 [Abstract] [Full Text]  
• Soltoff, S. P. (2001). Rottlerin Is a Mitochondrial Uncoupler That Decreases Cellular ATP Levels and Indirectly Blocks Protein Kinase Cdelta Tyrosine Phosphorylation. J. Biol. Chem. 276: 37986-37992 [Abstract] [Full Text]  
• Konishi, H., Yamauchi, E., Taniguchi, H., Yamamoto, T., Matsuzaki, H., Takemura, Y., Ohmae, K., Kikkawa, U., Nishizuka, Y. (2001). Phosphorylation sites of protein kinase C delta in H2O2-treated cells and its activation by tyrosine kinase invitro. Proc. Natl. Acad. Sci. USA 98: 6587-6592 [Abstract] [Full Text]