Ras GTPase-activating protein: a substrate and a potential binding protein of the protein-tyrosine kinase p56lck.

AUTOR(ES)

Amrein, K E

RESUMO

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.

Documentos Relacionados

• Protein-tyrosine kinases regulate the phosphorylation, protein interactions, subcellular distribution, and activity of p21ras GTPase-activating protein.
• The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck.
• The nonreceptor protein-tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src.
• p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.
• Purification and initial characterization of the lymphoid-cell protein-tyrosine kinase p56lck from a baculovirus expression system.