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 Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vogel, L B Articles by Fujita, D J Search for Related Content PubMed PubMed Citation Articles by Vogel, L B Articles by Fujita, D J

 Previous Article  |  Next Article 

Mol Cell Biol. 1993 December; 13(12): 7408-7417

The SH3 domain of p56lck is involved in binding to phosphatidylinositol 3'-kinase from T lymphocytes.

Department of Medical Biochemistry, University of Calgary Medical Centre, Alberta, Canada.

ABSTRACT

Many of the Src-like tyrosine kinases are thought to participate in multiprotein complexes that modulate transmembrane signalling through tyrosine phosphorylation. We have used in vitro binding studies employing bacterially expressed glutathione S-transferase-p56lck fusion proteins and cell extracts to map regions on p56lck that are involved in binding to phosphatidylinositol 3'-kinase (PI3K). Deletions within the SH3 domain of p56lck abolished binding of PI3K activity from T-cell lysates, whereas deletion of the SH2 domain caused only a slight reduction in the level of PI3K activity bound to p56lck sequences. The binding of PI3K from T-cell extracts to p56lck was not blocked by antiphosphotyrosine antibodies, but p56lck-bound PI3K activity was sensitive to phosphatase treatment. The SH3 domain of p56lck also bound the majority of PI3K activity from uninfected chicken embryo fibroblasts. However, a drastically different binding specificity was observed with use of extracts of Rous sarcoma virus v-src-transformed cells, in which the majority of PI3K activity bound to the SH2 domain of p56lck in a phosphotyrosine-dependent manner. These results suggest that are two modes of PI3K binding to p56lck, and presumably to other Src-like tyrosine kinases. In one mode, PI3K from T cells or uninfected chicken embryo fibroblasts binds predominantly to the SH3 domain of p56lck. In the other mode, involving PI3K from Rous sarcoma virus-transformed cells, binding is largely phosphotyrosine dependent and requires the SH2 domain of p56lck.

This article has been cited by other articles:

• Scott, M. P., Zappacosta, F., Kim, E. Y., Annan, R. S., Miller, W. T. (2002). Identification of Novel SH3 Domain Ligands for the Src Family Kinase Hck. WISKOTT-ALDRICH SYNDROME PROTEIN (WASP), WASP-INTERACTING PROTEIN (WIP), AND ELMO1. J. Biol. Chem. 277: 28238-28246 [Abstract] [Full Text]  
• Eckenberg, R., Moreau, J.-L., Melnyk, O., Theze, J. (2000). IL-2R{beta} Agonist P1-30 Acts in Synergy with IL-2, IL-4, IL-9, and IL-15: Biological and Molecular Effects. J. Immunol. 165: 4312-4318 [Abstract] [Full Text]  
• Suprynowicz, F. A., Sparkowski, J., Baege, A., Schlegel, R. (2000). E5 Oncoprotein Mutants Activate Phosphoinositide 3-Kinase Independently of Platelet-derived Growth Factor Receptor Activation. J. Biol. Chem. 275: 5111-5119 [Abstract] [Full Text]  
• Takemoto, Y., Furuta, M., Sato, M., Kubo, M., Hashimoto, Y. (1999). Isolation and characterization of a novel HS1 SH3 domain binding protein, HS1BP3. Int Immunol 11: 1957-1964 [Abstract] [Full Text]  
• Choi, Y. B., Kim, C. K., Yun, Y. (1999). Lad, an Adapter Protein Interacting with the SH2 Domain of p56lck, Is Required for T Cell Activation ,2. J. Immunol. 163: 5242-5249 [Abstract] [Full Text]  
• Sahuquillo, A. G., Roumier, A., Teixeiro, E., Bragado, R., Alarcon, B. (1998). T Cell Receptor (TCR) Engagement in Apoptosis-defective, but Interleukin 2 (IL-2)-producing, T Cells Results in Impaired ZAP70/CD3-zeta Association. J. Exp. Med. 187: 1179-1192 [Abstract] [Full Text]  
• Geltz, N. R., Augustine, J. A. (1998). The p85 and p110 Subunits of Phosphatidylinositol 3-Kinase-alpha Are Substrates, In Vitro, for a Constitutively Associated Protein Tyrosine Kinase in Platelets. Blood 91: 930-939 [Abstract] [Full Text]  
• August, A., Sadra, A., Dupont, B., Hanafusa, H. (1997). Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase. Proc. Natl. Acad. Sci. USA 94: 11227-11232 [Abstract] [Full Text]  
• Luo, X., Sando, J. J. (1997). Deficient Tyrosine Phosphorylation of c-Cbl and Associated Proteins in Phorbol Ester-resistant EL4 Mouse Thymoma Cells. J. Biol. Chem. 272: 12221-12228 [Abstract] [Full Text]  
• Trub, T., Frantz, J. D., Miyazaki, M., Band, H., Shoelson, S. E. (1997). The Role of a Lymphoid-restricted, Grb2-like SH3-SH2-SH3 Protein in T Cell Receptor Signaling. J. Biol. Chem. 272: 894-902 [Abstract] [Full Text]  
• August, A., Dupont, B. (1996). Association between Mitogen-activated Protein Kinase and the [IMAGE] Chain of the T Cell Receptor (TcR) with the SH2,3 Domain of p56[IMAGE]. J. Biol. Chem. 271: 10054-10059 [Abstract] [Full Text]  
• Pagès, F.ço., Ragueneau, M., Klasen, S., Battifora, M., Couez, D., Sweet, R., Truneh, A., Ward, S. G., Olive, D. (1996). Two Distinct Intracytoplasmic Regions of the T-cell Adhesion Molecule CD28 Participate in Phosphatidylinositol 3-Kinase Association. J. Biol. Chem. 271: 9403-9409 [Abstract] [Full Text]  
• Briggs, S. D., Bryant, S. S., Jove, R., Sanderson, S. D., Smithgall, T. E. (1995). The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck. J. Biol. Chem. 270: 14718-14724 [Abstract] [Full Text]  
• Haefner, B., Baxter, R., Fincham, V. J., Downes, C. P., Frame, M. C. (1995). Cooperation of Src Homology Domains in the Regulated Binding of Phosphatidylinositol 3-Kinase. J. Biol. Chem. 270: 7937-7943 [Abstract] [Full Text]  
• Vogel, L. B., Fujita, D. J. (1995). p70 Phosphorylation and Binding to p56[IMAGE] Is an Early Event in Interleukin-2-induced Onset of Cell Cycle Progression in T-lymphocytes. J. Biol. Chem. 270: 2506-2511 [Abstract] [Full Text]