Modification of Ser59in the Unique N-Terminal Region of Tyrosine Kinase p56lckRegulates Specificity of its Src Homology 2 Domain

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 13; pp. 5778 - 5782
• Main Authors: Joung, Insil, Kim, TaeUe, Stolz, Lesley A., Payne, Gillian, Winkler, David G., Walsh, Christopher T., Strominger, Jack L., Shin, Jaekyoon
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of the United States of America 20.06.1995
• Subjects: Antibodies; Biochemistry; Crosslinking; Goods and services tax; HeLa cells; Phosphatases; Phosphorylation; Physiological regulation; Proteins; T lymphocytes
• ISSN: 0027-8424; 1091-6490

During T-cell activation, Ser59in the unique N-terminal region of p56lckis phosphorylated. Mutation of Ser59to Glu59mimics Ser59phosphorylation, and upon CD4 crosslinking, this mutant p56lckinduces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56lck. Mutant and wild-type p56lckhave similar affinities for CD4 and similar kinase activities. In glutathione S-transferase fusion proteins, the p56lckSrc homology 2 (SH2) domain with the SH3 domain and the unique N-terminal region (including Ser59) has a different binding specificity for phosphotyrosyl proteins than the SH2 domain alone. Either deletion of the unique N-terminal region or mutation of Ser59to Glu59in the fusion protein reverts the phosphotyrosyl protein binding specificity back to that of the SH2 domain alone. These results suggest that phosphorylation of Ser59regulates the function of p56lckby controlling binding specificity of its SH2 domain.