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Mol Cell Biol. 1986 December; 6(12): 4467-4477

Dephosphorylation or antibody binding to the carboxy terminus stimulates pp60c-src.

ABSTRACT

Phosphorylation of pp60c-src at Tyr-527, six residues from the carboxy terminus, has been implicated in regulation of the protein-tyrosine kinase activity of pp60c-src. Here we show that dephosphorylation of pp60c-src by phosphatase treatment in vitro caused a 10- to 20-fold increase in pp60c-src protein-tyrosine kinase activity. Binding of specific antibody to the region of pp60c-src which contains phosphotyrosine-527 also increased kinase activity. Each treatment increased phosphorylation of added substrates and of Tyr-416 within pp60c-src by a similar mechanism that involved altered interactions with ATP and increased catalytic rate. We suggest that the phosphorylated carboxy terminus acts as an inhibitor of the protein kinase domain of pp60c-src, unless its conformation is altered by either dephosphorylation or antibody binding. The antibody additionally stimulated the phosphorylation of forms of pp60c-src that had reduced gel mobility, much like those phosphorylated in kinase reactions containing pp60c-src activated by polyomavirus medium tumor antigen. These in vitro experiments provide models for the activation of pp60c-src in cells transformed by polyomavirus. We also show that autophosphorylation of pp60c-src at Tyr-527 occurs only to a very limited extent in vitro, even when Tyr-527 is made available for phosphorylation by treatment with phosphatase. This suggests that other protein-tyrosine kinases may normally phosphorylate Tyr-527 and regulate pp60c-src in the cell.

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• Corey, S. J., Anderson, S. M. (1999). Src-Related Protein Tyrosine Kinases in Hematopoiesis. Blood 93: 1-14 [Full Text]  
• Arregui, C. O., Balsamo, J., Lilien, J. (1998). Impaired Integrin-mediated Adhesion and Signaling in Fibroblasts Expressing a Dominant-negative Mutant PTP1B. J. Cell Biol. 143: 861-873 [Abstract] [Full Text]  
• DeMali, K. A., Kazlauskas, A. (1998). Activation of Src Family Members Is Not Required for the Platelet-Derived Growth Factor beta  Receptor To Initiate Mitogenesis. Mol. Cell. Biol. 18: 2014-2022 [Abstract] [Full Text]  
• Somani, A.-K., Bignon, J. S., Mills, G. B., Siminovitch, K. A., Branch, D. R. (1997). Src Kinase Activity Is Regulated by the SHP-1 Protein-tyrosine Phosphatase. J. Biol. Chem. 272: 21113-21119 [Abstract] [Full Text]  
• Weijland, A., Williams, J. C., Neubauer, G., Courtneidge, S. A., Wierenga, R. K., Superti-Furga, G. (1997). Src regulated by C-terminal phosphorylation is monomeric. Proc. Natl. Acad. Sci. USA 94: 3590-3595 [Abstract] [Full Text]  
• Marie-Cardine, A., Fischer, S., Gorvel, J.-P., Maridonneau-Parini, I. (1996). Recruitment of Activated p56lck on Endosomes of CD2-triggered T Cells, Colocalization with ZAP-70. J. Biol. Chem. 271: 20734-20739 [Abstract] [Full Text]  
• Allen, P. B., Wiedemann, L. M. (1996). An Activating Mutation in the ATP Binding Site of the ABL Kinase Domain. J. Biol. Chem. 271: 19585-19591 [Abstract] [Full Text]  
• Alexandropoulos, K, Baltimore, D (1996). Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel p130Cas-related protein, Sin.. Genes Dev. 10: 1341-1355 [Abstract]  
• Stover, D. R., Furet, P., Lydon, N. B. (1996). Modulation of the SH2 Binding Specificity and Kinase Activity of Src by Tyrosine Phosphorylation within Its SH2 Domain. J. Biol. Chem. 271: 12481-12487 [Abstract] [Full Text]  
• Catipovic, B., Schneck, J. P., Brummet, M. E., Marsh, D. G., Rafnar, T. (1996). Csk Is Constitutively Associated with a 60-kDa Tyrosine-phosphorylated Protein in Human T Cells. J. Biol. Chem. 271: 9698-9703 [Abstract] [Full Text]  
• Kawakatsu, H., Sakai, T., Takagaki, Y., Shinoda, Y., Saito, M., Owada, M. K., Yano, J. (1996). A New Monoclonal Antibody Which Selectively Recognizes the Active Form of Src Tyrosine Kinase. J. Biol. Chem. 271: 5680-5685 [Abstract] [Full Text]  
• Stoker, A., Gehrig, B, Haj, F, Bay, B. (1995). Axonal localisation of the CAM-like tyrosine phosphatase CRYP alpha: a signalling molecule of embryonic growth cones. Development 121: 1833-1844 [Abstract]  
• Boschelli, F, Uptain, S., Lightbody, J. (1993). The lethality of p60v-src in Saccharomyces cerevisiae and the activation of p34CDC28 kinase are dependent on the integrity of the SH2 domain. J. Cell Sci. 105: 519-528 [Abstract]  
• Piepenhagen, P., Nelson, W. (1993). Defining E-cadherin-associated protein complexes in epithelial cells: plakoglobin, beta- and gamma-catenin are distinct components. J. Cell Sci. 104: 751-762 [Abstract]  
• Thomas, J., Soriano, P, Brugge, J. (1991). Phosphorylation of c-Src on tyrosine 527 by another protein tyrosine kinase. Science 254: 568-571 [Abstract]  
• Brugge, J, Cotton, P, Lustig, A, Yonemoto, W, Lipsich, L, Coussens, P, Barrett, J N, Nonner, D, Keane, R W (1987). Characterization of the altered form of the c-src gene product in neuronal cells.. Genes Dev. 1: 287-296 [Abstract]