| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Previous Article | Next Article ![]()
Molecular and Cellular Biology, June 2007, p. 4406-4415, Vol. 27, No. 12
0270-7306/07/$08.00+0 doi:10.1128/MCB.02109-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Laboratory for Cell Signaling,1 Laboratory for Autoimmune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan,2 Center for Immunology, Washington University School of Medicine, St. Louis, Missouri,3 Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Marseille, France4
Received 10 November 2006/ Returned for modification 14 December 2006/ Accepted 30 March 2007
| ABSTRACT |
|---|
|
|
|---|
receptor I (Fc
RI). Although we have shown that protein tyrosine kinase Syk and sustained extracellular signal-regulated kinase (Erk) activation are required for IgE-induced mast cell survival, how Syk couples with sustained Erk activation is still unclear. Here, we report that the transmembrane adaptors LAT and NTAL are phosphorylated slowly upon IgE stimulation and that sustained but not transient Erk activation induced by IgE was inhibited in LAT/ NTAL/ bone marrow-derived mast cells (BMMCs). IgE-induced survival requires Ras activation, and both were impaired in LAT/ NTAL/ BMMCs. Sos was preferentially required for Fc
RI signals by IgE rather than IgE plus Ag. Survival impaired in LAT/ NTAL/ BMMCs was restored to levels comparable to those of the wild type by membrane-targeted Sos, which bypasses the Grb2-mediated membrane recruitment of Sos. The IgE-induced survival of BMMCs lacking Gads, an adaptor critical for the formation of the LAT-SLP-76-phospholipase C
(PLC
) complex, was observed to be normal. IgE stimulation induced the membrane retention of Grb2-green fluorescent protein fusion proteins in wild-type but not LAT/ NTAL/ BMMCs. These results suggest that LAT and NTAL contribute to the maintenance of Erk activation and survival through the membrane retention of the Ras-activating complex Grb2-Sos and, further, that the LAT-Gads-SLP-76-PLC
and LAT/NTAL-Grb2-Sos pathways are differentially required for degranulation and survival, respectively. | INTRODUCTION |
|---|
|
|
|---|
receptor I (Fc
RI), is usually considered to be a passive step called sensitization. However, recent studies have shown that IgE actively promotes several mast cell responses, such as survival, adhesion, and the promotion of in vivo inflammatory reactions in the absence of antigen (Ag) (3, 6, 16, 17, 26). Furthermore, high concentrations of IgE (>10 µg/ml) in the plasma of subjects with parasitic infections or atopic diseases have often been observed (18), suggesting a possible Ag-independent contribution of IgE to the exacerbation of these diseases. Recent studies have suggested that IgE may elicit weak Fc
RI aggregation to induce mast cell responses, even in the absence of multivalent Ag (22, 23). IgE-induced responses in the presence and absence of Ag are known to utilize distinct signaling pathways; by manipulating the duration of extracellular signal-regulated kinase (Erk) activation, we previously showed that sustained Erk activation is critical for mast cell survival but not for degranulation (52). Although we and others have also found that IgE-induced mast cell survival requires Fc receptor
-ITAM, Lyn, and Syk (21, 22, 24, 40), the molecular mechanism underlying the coupling of Syk with sustained Erk activation is still unclear.
Many reports have demonstrated that the duration of Erk activation alters the quality of biological responses (29, 30, 52). In a variety of receptor systems, Erk activation is regulated by Ras through the subsequent activation of Raf and mitogen-activated protein kinase/Erk kinase (MEK). Although Ras is activated by guanine nucleotide exchange factors (GEFs) such as Sos upon growth factor stimulation (7), recent reports have suggested that another GEF, RasGRP, also activates Ras in T-cell receptor (TCR)- or B-cell receptor (BCR)-mediated signaling (10, 32). RasGRP is activated by diacylglycerol, a product of phospholipase C
(PLC
)-mediated hydrolysis (11), providing a new pathway for Ras activation from Ag receptors. However, the contributions of Sos and RasGRP to Fc
RI signaling through IgE in the presence and absence of Ag are still unknown.
NTAL (5), also called LAB (15), and LAT are raft-localized transmembrane adaptor molecules possessing multiple tyrosine-based activation motifs, and they are the substrates for Syk (13, 36). Although Grb2 and Gads binding motifs are conserved in both proteins, the binding site for PLC
is present only in LAT and not in NTAL (5, 8, 14). It has been demonstrated previously that LAT is critical for mast cell activation upon IgE stimulation in the presence of Ag (38). On the other hand, NTAL has been reported to function as a negative regulator as well as a positive regulator of Fc
RI signaling in mast cells upon IgE-Ag stimulation (43, 47, 57). The analysis of bone marrow-derived mast cells (BMMCs) has led to the proposal of a possible mechanism for the molecular competition between the two proteins within the lipid raft, which may explain how NTAL exerts a negative regulatory function in a LAT-dependent manner (47, 57).
Using BMMCs deficient in both LAT and NTAL, we showed that these two adaptors contribute to IgE-induced sustained Erk activation and survival by acting as a scaffold for the retention of the Grb2-Sos complex within the plasma membrane.
| MATERIALS AND METHODS |
|---|
|
|
|---|
Abs.
The mouse anti-dinitrophenol IgE antibody (Ab) H1-DNP-
-26 was kindly provided by F.-T. Liu and T. Kawakami (La Jolla Institute, Ontario, CA) and used for survival assays. The mouse antidinitrophenol IgE Ab SPE-7 was purchased from Sigma (St. Louis, MO) and used for survival assays and biochemistry analyses. For IgE stimulation, each IgE clone was ultracentrifuged at 100,000 x g for 10 min just before use in the assays in order to exclude aggregates, as described previously (24, 33). Anti-phospho-Erk Ab was purchased from Promega (Madison, WI), anti-phospho-Syk was from Cell Signaling Technology (Beverly, MA), antiactin was obtained from Sigma, anti-phospho-PLC
was from Biosource International (Camarillo, CA), anti-Ras was purchased from Pierce Biotechnology (Rockford, IL), anti-green fluorescent protein (anti-GFP) was obtained from Invitrogen (Carlsbad, CA), anti-GFP-horseradish peroxidase (HRP) was from Miltenyi Biotec (Bergisch, Gladbach, Germany), anti-mouse IgG-HRP and protein G-Sepharose were purchased from Amersham Biosciences (Piscataway, NJ), anti-rabbit Ig-HRP was from Zymed (San Francisco, CA), and anti-Sos Ab was obtained from BD Pharmingen (San Diego, CA). Anti-mCD63 monoclonal Ab, which has been proven to be specific to CD63 by using CD63 transfectant, was kindly provided by K. Nishida (RIKEN, Yokohama, Japan). Anti-NTAL Abs were kindly provided by V. Horejsi (Academy of Science of the Czech Republic, Prague).
Construction. To construct the Grb2-GFP fusion, the Grb2 gene was fused to that for GFP by PCR. Genes for RasN17 and farnesylated Sos, which were kindly provided by K. Nishida (RIKEN, Yokohama, Japan) and A. Aronheim (Israel Institute of Technology, Haifa, Israel) (1), respectively, were cloned into the pMX-IRES-hCD8 (53) or pMX-IRES-GFP retroviral vector. Glutathione S-transferase (GST)-Raf-Ras binding domain (RBD) was kindly provided by J. L. Bos (University Medical Center Utrecht, Utrecht, The Netherlands) (9). For the construct comprising the proline-rich domains of Sos (Sos-Pro), the region of the Sos gene corresponding to amino acids 1,019 to 1,336 was amplified by PCR and subcloned into pMX-IRES-GFP (20).
Retroviral infection and BMMC induction.
The preparation of BMMCs and fetal liver-derived mast cells and the retroviral infection of BMMCs were carried out as previously described (24, 52). Adherent cells were removed every 3 to 5 days. After 4 weeks, homogeneous populations of Fc
RI-positive, c-kit-positive BMMCs were obtained. For the infection of differentiated BMMCs, cells were cultured with 100 ng of stem cell factor/ml and 30 ng of interleukin-3 (IL-3)/ml for 12 h and then spin infected with concentrated virus supernatant.
Western blotting. BMMCs were cultured without IL-3 for 2 h and then stimulated with IgE (SPE-7) at 37°C for the times indicated below. Cells were lysed in lysis buffer containing 1% Nonidet P-40 and subjected to Western blotting as previously described (52).
Survival assays.
BMMCs (2 x 105) were washed with IL-3-free medium twice and then stimulated with IgE (H1-DNP-
-26 and SPE-7) in 400 µl of IL-3-free medium on 48-well plates. Forty-microliter samples of the cultured cells were taken daily and stained with propidium iodide, and live cells were counted with a FACSCalibur flow cytometer (BD Biosciences, San Jose, CA). Live-cell gating was performed on FL3 (propidium iodide)-side-scatter dot plots, which can separate out live cell populations clearly.
Real-time reverse transcription-PCR (RT-PCR). BMMCs were incubated in the absence of IL-3 for 1 h and then stimulated with IgE for 1 h. RNA was isolated by using an RNeasy minikit (QIAGEN, Valencia, CA). After the removal of genomic DNA by treatment with DNase (Wako Nippon Gene, Tokyo, Japan), randomly primed cDNA strands were generated with reverse transcriptase II (Invitrogen). By using gene-specific primers, RNA expression was quantified by real-time PCR, and values were normalized to ß-actin expression. Gene-specific primer sequences were as follows: ß-actin gene, 5'-TGGAATCCTGTGGCATCCATGAAAC-3' (forward) and 5'-TAAAACGCAGCTCAGTAACAGTCCG-3' (reverse); IL-3 gene, 5'-ATAGGGAAGCTCCCAGAACCTGAACTC-3' (forward) and 5'-AGACCCCTGGCAGCGCAGAGTCATTC-3' (reverse); and histidine decarboxylase gene, 5'-AGTCTGGCGAGAAGGGAAGG-3' (forward) and 5'-TCTGGGCACTCATAGGCACA-3' (reverse).
Pulldown assay. BMMCs were lysed with lysis buffer (Ras activation kit; Pierce, Rockford, IL). Cell lysates were incubated with GST-Raf-RBD-bound glutathione-Sepharose for 1 h at 4°C. After the samples had been washed five times with lysis buffer, Sepharose-bound protein was eluted with 10 mM glutathione and analyzed by Western blotting with anti-Ras Ab.
Flow cytometric analysis of degranulation. Degranulation was analyzed by flow cytometry as described previously (31). Briefly, BMMCs were sensitized with 1 µg of IgE (SPE-7)/ml for 4 h and then stimulated with 50 ng of dinitrophenol-conjugated human serum albumin (DNP-HSA)/ml for 30 min in Tyrode's buffer. Cells were fixed with 4% paraformaldehyde for 15 min and then stained with anti-CD63 Ab and phycoerythrin-conjugated goat anti-mouse IgG (heavy- and light-chain) Fab (Cedarlane, Ontario, Canada). The surface expression of CD63 was determined by flow cytometry.
Microscopic analysis. BMMCs were infected with pMX-Grb2/GFP-IRES-hCD8. After being sorted with anti-human CD8 (anti-hCD8), the cells were stimulated with immobilized IgE (SPE-7; 10 µg/ml) on a glass-coated dish (Mat-Tech, Ashland, MA). After 30 min of incubation at 37°C, the cells were analyzed by wide-field fluorescence microscopy with an IX-81 instrument (Olympus, Tokyo, Japan). The membrane localization of Grb2-GFP was assessed by total internal reflection fluorescence (TIRF) microscopy with an IX81-ARCEVA system (Olympus, Tokyo, Japan).
| RESULTS |
|---|
|
|
|---|
|
RI in BMMCs (data not shown), consistent with results in previous reports (47, 57). We compared the kinetics of downstream signaling in these BMMCs after stimulation by IgE in the absence of Ag (Fig. 2A, B, and C) and in the presence of Ag (Fig. 2D). Although LAT plays a critical role in IgE-induced mast cell responses in the presence of Ag (38), sustained Erk activation by IgE in LAT/ BMMCs was slightly reduced but still observed. In contrast, dKO BMMCs showed severe impairment of sustained Erk activation, although transient activation was almost normal (Fig. 2A and B). A minor role for LAT and NTAL in transient Erk activation was also evident upon Fc
RI stimulation by Ag cross-linking (Fig. 2D) (57). The intensity of Erk activation in NTAL/ BMMCs was augmented (Fig. 2A and B), consistent with the reports that NTAL negatively regulates mast cell responses induced by IgE in the presence of Ag (47, 57). The level of Syk phosphorylation, as an upstream event, in dKO BMMCs was not decreased (Fig. 2C). These results indicate that IgE-induced Erk activation can be triggered but not sustained in the absence of LAT and NTAL even when Fc
RI engagement and Syk activation are prolonged.
|
|
|
To verify if Sos also contributes to the IgE-mediated signal in the presence of Ag, we examined the effect of Sos-Pro on degranulation induced by IgE in the presence of Ag by analyzing CD63 expression on the cell surface as a marker for degranulation (31). Surprisingly, the levels of induction of surface CD63 expression in GFP-negative (control) and GFP-positive (Sos-Pro) cells were similar (Fig. 4F). Thus, in the absence of Ag the Sos-Ras pathway is preferentially required for IgE-induced events as a downstream component of LAT and NTAL.
The Gads-mediated pathway is not essential for IgE-induced mast cell survival.
In addition to Grb2, LAT and NTAL can bind Gads, an adaptor molecule that is similar to Grb2 and contains Src homology 3 (SH3)-SH2-SH3 domains. Gads is essential for linking LAT and SLP-76 (2) and is critical for TCR-mediated PLC
1 activation and Ca2+ influx (56). It was recently reported that PLC
also contributes to Ras activation through RasGRP, a diacylglycerol-dependent GEF. To examine the contribution of the Gads-mediated pathway to IgE-induced responses in the absence of Ag, we analyzed Gads/ BMMCs. PLC
activation in Gads/ BMMCs was impaired, as expected (Fig. 5A). However, levels of sustained Erk activation, Ras activation, and mast cell survival in Gads/ BMMCs were observed to be comparable to those in WT BMMCs (Fig. 5). Thus, although LAT and NTAL can potentially bind both Grb2 and Gads, Gads seems to play a minor role in IgE-induced sustained Erk activation and mast cell survival in the absence of Ag. In contrast, we recently found that IgE-induced degranulation in the presence of Ag in Gads/ mice is impaired (S. Yamasaki, O. Kanagawa, and T. Saito, unpublished data).
|
|
| DISCUSSION |
|---|
|
|
|---|
RI without internalization may induce sustained Erk activation through prolonged Fc
RI ligation (23, 52, 54). Nevertheless, even when Fc
RI engagement and Syk activation were prolonged, sustained Erk activation in LAT/ NTAL/ BMMCs was almost completely inhibited, suggesting that the two adaptors LAT and NTAL constitute some kind of timer for downstream signaling. Note that transient Erk activation was not dramatically impaired by IgE stimulation in the absence of Ag (Fig. 2A and B) and in the presence of Ag (Fig. 2D) (57) in the absence of LAT and NTAL. This result suggests that transient Erk activation via Fc
RI is LAT- and NTAL-independent and that the weak and prolonged cross-linking of Fc
RI may preferentially utilize LAT and NTAL for sustained Erk activation, eventually leading to mast cell survival. However, so far we cannot directly exclude the possible contribution of another pathway to sustained Erk activation, such as the activation of Rap1, B-Raf, or protein kinase C, as reported previously (19, 41, 45).
Oh-hora et al. showed the differential requirements for RasGRP and Sos in BCR- and epidermal growth factor receptor-mediated Ras activation, respectively, by using chicken B-cell lines (32). Our observation that dominant negative Sos suppresses IgE-mediated survival in the absence of Ag but not IgE-induced degranulation in the presence of Ag implies the existence of similar divergence patterns in Fc
RI signaling; weak, constitutive engagement but not Ag cross-linking of Fc
RI may result in the preferential utilization of Sos rather than RasGRP for Ras activation. Although RasGRP4 is expressed in mast cells (55), the lack of Gads or LATimportant in regulating PLC
through the formation of the LAT-Gads-SLP-76-PLC
quaternary complex (27, 42, 51)did not result in severe impairment of sustained Erk activation, suggesting that PLC
-dependent RasGRP4 activation may not play a major role in the maintenance of IgE-induced signals in mast cells in the absence of Ag. Considering that LAT/ mice exhibited severe impairment of IgE-induced mast cell degranulation in the presence of Ag (38, 57), NTAL appears to compensate for LAT function preferentially under stimulation via IgE without Ag. This finding may be explained by the fact that NTAL possesses binding sites for Grb2 but not for PLC
, which is crucial for degranulation (48, 49). Consistent with this suggestion, Y136, a PLC
binding site of LAT, has been shown to be essential for degranulation (28, 39).
Recently, accumulating evidence has suggested that the quantity and duration of signals through immune receptors determine distinct immune responses (29, 50). It is attractive to speculate that, likewise, the differential contributions of Sos and RasGRP are also operative in Ras activation during sustained Ag receptor triggering, for example, during the tonic signal of BCR (25), TCR engagement for homeostatic proliferation (12), or autonomous pre-TCR signaling (53). Indeed, RasGRP1-deficient thymocytes display no apparent defect in autonomous pre-TCR signaling, a process that is known to depend on Ras activation (10, 37).
The augmentation of mast cell function by the genetic deletion of NTAL alone has been explained by an increase in the amount of available LAT (47, 57), in light of the possible competition between the two transmembrane adaptors within the lipid raft. In line with these speculations, IgE-induced events in the absence of Ag are also upregulated in NTAL/ BMMCs. As an additional possible explanation, we found that specific chemokine receptors are constitutively upregulated in NTAL/ BMMCs (S. Yamasaki and T. Saito, unpublished data); this upregulation may also contribute to the augmented mast cell responses seen in NTAL-deficient single-knockout mice.
Taking these findings together, we propose herein a possible molecular mechanism by which Syk couples with sustained Erk activation upon IgE stimulation in the absence of Ag. IgE without Ag induces the delayed phosphorylation of LAT and NTAL. Phosphorylated LAT and NTAL may serve as a docking platform that enables the retention of the Grb2-Sos complex within the plasma membrane. Thus, Fc
RI can differentially utilize the intracellular signaling machinery in response to different stimuli, and the raft-localized membrane adaptors LAT and NTAL are the critical transducers for timing the duration of signals from Fc
RI to trigger downstream events. These results suggest that it may be possible to differentially modulate signaling events through Fc
RI in order to block specific allergic reactions.
| ACKNOWLEDGMENTS |
|---|
The development and characterization of NTAL-deficient mice were supported by FRM (Defis de la Recherche en Allergologie). This study was supported by a grant-in-aid for priority area research (A) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
| FOOTNOTES |
|---|
Published ahead of print on 9 April 2007. ![]()
| REFERENCES |
|---|
|
|
|---|
2. Asada, H., N. Ishii, Y. Sasaki, K. Endo, H. Kasai, N. Tanaka, T. Takeshita, S. Tsuchiya, T. Konno, and K. Sugamura. 1999. Grf40, a novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT. J. Exp. Med. 189:1383-1390.
3. Asai, K., J. Kitaura, Y. Kawakami, N. Yamagata, M. Tsai, D. P. Carbone, F. T. Liu, S. J. Galli, and T. Kawakami. 2001. Regulation of mast cell survival by IgE. Immunity 14:791-800.[CrossRef][Medline]
4. Axelrod, D. 1981. Cell-substrate contacts illuminated by total internal reflection fluorescence. J. Cell Biol. 89:141-145.
5. Brdicka, T., M. Imrich, P. Angelisova, N. Brdickova, O. Horvath, J. Spicka, I. Hilgert, P. Luskova, P. Draber, P. Novak, N. Engels, J. Wienands, L. Simeoni, J. Osterreicher, E. Aguado, M. Malissen, B. Schraven, and V. Horejsi. 2002. Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling. J. Exp. Med. 196:1617-1626.
6. Bryce, P. J., M. L. Miller, I. Miyajima, M. Tsai, S. J. Galli, and H. C. Oettgen. 2004. Immune sensitization in the skin is enhanced by antigen-independent effects of IgE. Immunity 20:381-392.[CrossRef][Medline]
7. Chardin, P., J. H. Camonis, N. W. Gale, L. van Aelst, J. Schlessinger, M. H. Wigler, and D. Bar-Sagi. 1993. Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Science 260:1338-1343.
8. Cho, S., C. A. Velikovsky, C. P. Swaminathan, J. C. Houtman, L. E. Samelson, and R. A. Mariuzza. 2004. Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads. EMBO J. 23:1441-1451.[CrossRef][Medline]
9. de Rooij, J., and J. L. Bos. 1997. Minimal Ras-binding domain of Raf1 can be used as an activation-specific probe for Ras. Oncogene 14:623-625.[CrossRef][Medline]
10. Dower, N. A., S. L. Stang, D. A. Bottorff, J. O. Ebinu, P. Dickie, H. L. Ostergaard, and J. C. Stone. 2000. RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nat. Immunol. 1:317-321.[CrossRef][Medline]
11. Ebinu, J. O., D. A. Bottorff, E. Y. Chan, S. L. Stang, R. J. Dunn, and J. C. Stone. 1998. RasGRP, a Ras guanyl nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Science 280:1082-1086.
12. Goldrath, A. W., and M. J. Bevan. 1999. Selecting and maintaining a diverse T-cell repertoire. Nature 402:255-262.[CrossRef][Medline]
13. Horejsi, V. 2004. Transmembrane adaptor proteins in membrane microdomains: important regulators of immunoreceptor signaling. Immunol. Lett. 92:43-49.[CrossRef][Medline]
14. Janssen, E., M. Zhu, B. Craven, and W. Zhang. 2004. Linker for activation of B cells: a functional equivalent of a mutant linker for activation of T cells deficient in phospholipase C-
1 binding. J. Immunol. 172:6810-6819.
15. Janssen, E., M. Zhu, W. Zhang, and S. Koonpaew. 2003. LAB: a new membrane-associated adaptor molecule in B cell activation. Nat. Immunol. 4:117-123.[CrossRef][Medline]
16. Kalesnikoff, J., M. Huber, V. Lam, J. E. Damen, J. Zhang, R. P. Siraganian, and G. Krystal. 2001. Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity 14:801-811.[CrossRef][Medline]
17. Kawakami, T., and S. J. Galli. 2002. Regulation of mast-cell and basophil function and survival by IgE. Nat. Rev. Immunol. 2:773-786.[CrossRef][Medline]
18. Kawakami, T., and J. Kitaura. 2005. Mast cell survival and activation by IgE in the absence of antigen: a consideration of the biologic mechanisms and relevance. J. Immunol. 175:4167-4173.
19. Kawakami, Y., J. Kitaura, L. Yao, R. W. McHenry, A. C. Newton, S. Kang, R. M. Kato, M. Leitges, D. J. Rawlings, and T. Kawakami. 2003. A Ras activation pathway dependent on Syk phosphorylation of protein kinase C. Proc. Natl. Acad. Sci. USA 100:9470-9475.
20. Kitamura, T. 1998. New experimental approaches in retrovirus-mediated expression screening. Int. J. Hematol. 67:351-359.[CrossRef][Medline]
21. Kitaura, J., K. Eto, T. Kinoshita, Y. Kawakami, M. Leitges, C. A. Lowell, and T. Kawakami. 2005. Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases. J. Immunol. 174:4495-4504.
22. Kitaura, J., J. Song, M. Tsai, K. Asai, M. Maeda-Yamamoto, A. Mocsai, Y. Kawakami, F. T. Liu, C. A. Lowell, B. G. Barisas, S. J. Galli, and T. Kawakami. 2003. Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the Fc
RI. Proc. Natl. Acad. Sci. USA 100:12911-12916.
23. Kitaura, J., W. Xiao, M. Maeda-Yamamoto, Y. Kawakami, C. A. Lowell, and T. Kawakami. 2004. Early divergence of Fc
receptor I signals for receptor up-regulation and internalization from degranulation, cytokine production, and survival. J. Immunol. 173:4317-4323.
24. Kohno, M., S. Yamasaki, V. L. Tybulewicz, and T. Saito. 2005. Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen. Blood 105:2059-2065.
25. Lam, K. P., R. Kuhn, and K. Rajewsky. 1997. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90:1073-1083.[CrossRef][Medline]
26. Lam, V., J. Kalesnikoff, C. W. Lee, V. Hernandez-Hansen, B. S. Wilson, J. M. Oliver, and G. Krystal. 2003. IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE+ antigen but distinct from those used by Steel factor. Blood 102:1405-1413.
27. Lin, J., and A. Weiss. 2001. Identification of the minimal tyrosine residues required for linker for activation of T cell function. J. Biol. Chem. 276:29588-29595.
28. Malbec, O., M. Malissen, I. Isnardi, R. Lesourne, A. M. Mura, W. H. Fridman, B. Malissen, and M. Daeron. 2004. Linker for activation of T cells integrates positive and negative signaling in mast cells. J. Immunol. 173:5086-5094.
29. Mariathasan, S., A. Zakarian, D. Bouchard, A. M. Michie, J. C. Zuniga-Pflucker, and P. S. Ohashi. 2001. Duration and strength of extracellular signal-regulated kinase signals are altered during positive versus negative thymocyte selection. J. Immunol. 167:4966-4973.
30. Marshall, C. J. 1995. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:179-185.[CrossRef][Medline]
31. Nishida, K., S. Yamasaki, Y. Ito, K. Kabu, K. Hattori, T. Tezuka, H. Nishizumi, D. Kitamura, R. Goitsuka, R. S. Geha, T. Yamamoto, T. Yagi, and T. Hirano. 2005. Fc
RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane. J. Cell Biol. 170:115-126.
32. Oh-hora, M., S. Johmura, A. Hashimoto, M. Hikida, and T. Kurosaki. 2003. Requirement for Ras guanine nucleotide releasing protein 3 in coupling phospholipase C-
2 to Ras in B cell receptor signaling. J. Exp. Med. 198:1841-1851.
33. Pandey, V., S. Mihara, A. Fensome-Green, S. Bolsover, and S. Cockcroft. 2004. Monomeric IgE stimulates NFAT translocation into the nucleus, a rise in cytosol Ca2+, degranulation, and membrane ruffling in the cultured rat basophilic leukemia-2H3 mast cell line. J. Immunol. 172:4048-4058.
34. Pouyssegur, J., and P. Lenormand. 2003. Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Eur. J. Biochem. 270:3291-3299.[Medline]
35. Reif, K., L. Buday, J. Downward, and D. A. Cantrell. 1994. SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases. J. Biol. Chem. 269:14081-14087.
36. Rivera, J. 2005. NTAL/LAB and LAT: a balancing act in mast-cell activation and function. Trends Immunol. 26:119-122.[CrossRef][Medline]
37. Roose, J. P., M. Mollenauer, V. A. Gupta, J. Stone, and A. Weiss. 2005. A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol. Cell. Biol. 25:4426-4441.
38. Saitoh, S., R. Arudchandran, T. S. Manetz, W. Zhang, C. L. Sommers, P. E. Love, J. Rivera, and L. E. Samelson. 2000. LAT is essential for Fc
RI-mediated mast cell activation. Immunity 12:525-535.[CrossRef][Medline]
39. Saitoh, S., S. Odom, G. Gomez, C. L. Sommers, H. A. Young, J. Rivera, and L. E. Samelson. 2003. The four distal tyrosines are required for LAT-dependent signaling in F
RI-mediated mast cell activation. J. Exp. Med. 198:831-843.
40. Sakurai, D., S. Yamasaki, K. Arase, S. Y. Park, H. Arase, A. Konno, and T. Saito. 2004. F
RI
-ITAM is differentially required for mast cell function in vivo. J. Immunol. 172:2374-2381.
41. Sasagawa, S., Y. Ozaki, K. Fujita, and S. Kuroda. 2005. Prediction and validation of the distinct dynamics of transient and sustained ERK activation. Nat. Cell Biol. 7:365-373.[CrossRef][Medline]
42. Singer, A. L., S. C. Bunnell, A. E. Obstfeld, M. S. Jordan, J. N. Wu, P. S. Myung, L. E. Samelson, and G. A. Koretzky. 2004. Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J. Biol. Chem. 279:15481-15490.
43. Tkaczyk, C., V. Horejsi, S. Iwaki, P. Draber, L. E. Samelson, A. B. Satterthwaite, D. H. Nahm, D. D. Metcalfe, and A. M. Gilfillan. 2004. NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc
RI aggregation. Blood 104:207-214.
44. Tokunaga, M., K. Kitamura, K. Saito, A. H. Iwane, and T. Yanagida. 1997. Single molecule imaging of fluorophores and enzymatic reactions achieved by objective-type total internal reflection fluorescence microscopy. Biochem. Biophys. Res. Commun. 235:47-53.[CrossRef][Medline]
45. Tsukamoto, H., A. Irie, and Y. Nishimura. 2004. B-Raf contributes to sustained extracellular signal-regulated kinase activation associated with interleukin-2 production stimulated through the T cell receptor. J. Biol. Chem. 279:48457-48465.
46. van Biesen, T., B. E. Hawes, D. K. Luttrell, K. M. Krueger, K. Touhara, E. Porfiri, M. Sakaue, L. M. Luttrell, and R. J. Lefkowitz. 1995. Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature 376:781-784.[CrossRef][Medline]
47. Volna, P., P. Lebduska, L. Draberova, S. Simova, P. Heneberg, M. Boubelik, V. Bugajev, B. Malissen, B. S. Wilson, V. Horejsi, M. Malissen, and P. Draber. 2004. Negative regulation of mast cell signaling and function by the adaptor LAB/NTAL. J. Exp. Med. 200:1001-1013.
48. Wang, D., J. Feng, R. Wen, J. C. Marine, M. Y. Sangster, E. Parganas, A. Hoffmeyer, C. W. Jackson, J. L. Cleveland, P. J. Murray, and J. N. Ihle. 2000. Phospholipase C
2 is essential in the functions of B cell and several Fc receptors. Immunity 13:25-35.[CrossRef][Medline]
49. Wen, R., S. T. Jou, Y. Chen, A. Hoffmeyer, and D. Wang. 2002. Phospholipase C
2 is essential for specific functions of Fc
R and Fc
R. J. Immunol. 169:6743-6752.
50. Werlen, G., B. Hausmann, D. Naeher, and E. Palmer. 2003. Signaling life and death in the thymus: timing is everything. Science 299:1859-1863.
51. Yablonski, D., T. Kadlecek, and A. Weiss. 2001. Identification of a phospholipase C-
1 (PLC-
1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-
1 and NFAT. Mol. Cell. Biol. 21:4208-4218.
52. Yamasaki, S., E. Ishikawa, M. Kohno, and T. Saito. 2004. The quantity and duration of FcR
signals determine mast cell degranulation and survival. Blood 103:3093-3101.
53. Yamasaki, S., E. Ishikawa, M. Sakuma, K. Ogata, K. Sakata-Sogawa, M. Hiroshima, D. L. Wiest, M. Tokunaga, and T. Saito. 2006. Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development. Nat. Immunol. 7:67-75.[CrossRef][Medline]
54. Yamasaki, S., and T. Saito. 2005. Regulation of mast cell activation through F
RI. Chem. Immunol. Allergy 87:22-31.[Medline]
55. Yang, Y., L. Li, G. W. Wong, S. A. Krilis, M. S. Madhusudhan, A. Sali, and R. L. Stevens. 2002. RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function. J. Biol. Chem. 277:25756-25774.
56. Yoder, J., C. Pham, Y. M. Iizuka, O. Kanagawa, S. K. Liu, J. McGlade, and A. M. Cheng. 2001. Requirement for the SLP-76 adaptor GADS in T cell development. Science 291:1987-1991.
57. Zhu, M., Y. Liu, S. Koonpaew, O. Granillo, and W. Zhang. 2004. Positive and negative regulation of F
RI-mediated signaling by the adaptor protein LAB/NTAL. J Exp. Med. 200:991-1000.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| J. Bacteriol. | J. Virol. | Eukaryot. Cell |
|---|
| Microbiol. Mol. Biol. Rev. | Clin. Vaccine Immunol. | All ASM Journals |
|---|