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Science 18 March 1994:
Vol. 263. no. 5153, pp. 1609 - 1612
DOI: 10.1126/science.8128248

Articles

Science, Vol 263, Issue 5153, 1609-1612
Copyright © 1994 by American Association for the Advancement of Science


articles

Activation of phosphatidylinositol-3' kinase by Src-family kinase SH3 binding to the p85 subunit

CM Pleiman, WM Hertz, and JC Cambier

Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.

Engagement of antigen receptor complexes induces rapid activation of Src-family kinases and association with phosphatidylinositol-3' kinase (PI-3 kinase). Here it was found that the Src homology 3 (SH3) domain of Lyn and Fyn bound to a proline-rich region (residues 84 to 99) within the 85-kilodalton subunit (p85) of PI-3 kinase. The binding of SH3 to the purified kinase led to a five- to sevenfold increase in the specific activity of PI-3 kinase. Ligand-induced receptor stimulation activated PI-3 kinase, and this activation was blocked by a peptide containing residues 84 to 99 of p85. These data demonstrate a mechanism for PI-3 kinase activation and show that binding of SH3 domains to proline-rich target sequences can regulate enzymatic activity.


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   Abstract »    Full Text »    PDF »
Regulation of the p85/p110 Phosphatidylinositol 3'-Kinase: Stabilization and Inhibition of the p110alpha Catalytic Subunit by the p85 Regulatory Subunit.
J. Yu, Y. Zhang, J. McIlroy, T. Rordorf-Nikolic, G. A. Orr, and J. M. Backer (1998)
Mol. Cell. Biol. 18, 1379-1387
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A Role for CAP, a Novel, Multifunctional Src Homology 3 Domain-containing Protein in Formation of Actin Stress Fibers and Focal Adhesions.
V. Ribon, R. Herrera, B. K. Kay, and A. R. Saltiel (1998)
J. Biol. Chem. 273, 4073-4080
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Induction of Tyrosine Phosphorylation in Human MHC Class II-Positive Antigen-Presenting Cells by Stimulation with Contact Sensitizers.
U. Kuhn, P. Brand, J. Willemsen, H. Jonuleit, A. H. Enk, R. van Brandwijk-Petershans, J. Saloga, J. Knop, and D. Becker (1998)
J. Immunol. 160, 667-673
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Qualitative Regulation of B Cell Antigen Receptor Signaling by CD19: Selective Requirement for PI3-Kinase Activation, Inositol-1,4,5-Trisphosphate Production and Ca2+ Mobilization.
A. M. Buhl, C. M. Pleiman, R. C. Rickert, and J. C. Cambier (1997)
J. Exp. Med. 186, 1897-1910
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Src-induced activation of inducible T cell kinase (ITK) requires phosphatidylinositol 3-kinase activity and the Pleckstrin homology domain of inducible T cell kinase.
A. August, A. Sadra, B. Dupont, and H. Hanafusa (1997)
PNAS 94, 11227-11232
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Tyrosine Phosphorylation of the CD3-epsilon Subunit of the T Cell Antigen Receptor Mediates Enhanced Association with Phosphatidylinositol 3-Kinase in Jurkat T Cells.
I. de Aos, M. H. Metzger, M. Exley, C. E. Dahl, S. Misra, D. Zheng, L. Varticovski, C. Terhorst, and J. Sancho (1997)
J. Biol. Chem. 272, 25310-25318
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Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module.
A. E. Salcini, S. Confalonieri, M. Doria, E. Santolini, E. Tassi, O. Minenkova, G. Cesareni, P. G. Pelicci, and P. P. Di Fiore (1997)
Genes & Dev. 11, 2239-2249
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Phosphorylation of cbl after Stimulation of Nb2 Cells with Prolactin and Its Association with Phosphatidylinositol 3-Kinase.
S. Hunter, B. L. Koch, and S. M. Anderson (1997)
Mol. Endocrinol. 11, 1213-1222
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Differential Regulation of Phosphoinositide 3-Kinase Adapter Subunit Variants by Insulin in Human Skeletal Muscle.
P. R. Shepherd, B. T. Nave, J. Rincon, L. A. Nolte, A. P. Bevan, K. Siddle, J. R. Zierath, and H. Wallberg-Henriksson (1997)
J. Biol. Chem. 272, 19000-19007
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Molecular Cloning of SKAP55, a Novel Protein That Associates with the Protein Tyrosine Kinase p59fyn in Human T-lymphocytes.
A. Marie-Cardine, E. Bruyns, C. Eckerskorn, H. Kirchgessner, S. C. Meuer, and B. Schraven (1997)
J. Biol. Chem. 272, 16077-16080
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