Abstract
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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
B-Lymphocytes / enzymology*
-
Enzyme Activation
-
Lymphocyte Activation
-
Mice
-
Molecular Sequence Data
-
Peptide Fragments / pharmacology
-
Phosphatidylinositol 3-Kinases
-
Phosphotransferases (Alcohol Group Acceptor) / chemistry
-
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
-
Proline / chemistry
-
Protein-Tyrosine Kinases / chemistry
-
Protein-Tyrosine Kinases / metabolism*
-
Proto-Oncogene Proteins / chemistry
-
Proto-Oncogene Proteins / metabolism*
-
Proto-Oncogene Proteins c-fyn
-
src-Family Kinases*
Substances
-
Peptide Fragments
-
Proto-Oncogene Proteins
-
Proline
-
Phosphatidylinositol 3-Kinases
-
Phosphotransferases (Alcohol Group Acceptor)
-
Protein-Tyrosine Kinases
-
Fyn protein, mouse
-
Proto-Oncogene Proteins c-fyn
-
lyn protein-tyrosine kinase
-
src-Family Kinases