Open AccessRas GTPase-activating protein: a substrate and a potential binding protein of the protein-tyrosine kinase p56lck.
Author(s) -
Kurt E. Amrein,
Nicholas Flint,
Barbel Panholzer,
Paul Burn
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.8.3343
Subject(s) - gtpase activating protein , tyrosine phosphorylation , proto oncogene tyrosine protein kinase src , sh2 domain , receptor tyrosine kinase , sh3 domain , biology , tyrosine kinase , tyrosine , gtpase , microbiology and biotechnology , phosphorylation , protein tyrosine phosphatase , biochemistry , signal transduction , g protein
Ras GTPase-activating protein (GAP) is a cytoplasmic factor that regulates the GTPase activity of p21ras. Phosphorylation of GAP on tyrosine has recently been reported by several groups and may be an important step in linking signaling pathways involving p21ras and protein-tyrosine kinases. p56lck, a src-like protein-tyrosine kinase, seems to play a crucial role in T-cell development and T-cell activation. However, the molecular mechanisms of T-cell signaling involving p56lck and the substrates of p56lck have not yet been identified. To test whether GAP is a substrate of p56lck, in vitro kinase reactions were performed with purified, recombinant GAP and p56lck. We found that GAP became specifically phosphorylated on tyrosine within one tryptic peptide. Furthermore, coimmunoprecipitation studies provided evidence that the tyrosine-phosphorylated form of GAP is bound to p56lck. These results suggest that in T cells the function of GAP might be regulated through its phosphorylation on tyrosine and binding to the protein-tyrosine kinase p56lck.