Modification of Ser super(59) in the unique N-terminal region of tyrosine kinase p56 super(lck) regulates 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, I, Kim, TaeUe, Stolz, LA, Payne, G, Winkler, D G, Walsh, C T, Strominger, J L, Shin, J
• Format: Journal Article
• Language: English
• Published: 01.01.1995
• ISSN: 0027-8424

During T-cell activation, Ser super(59) in the unique N-terminal region of p56 super(lck) is phosphorylated. Mutation of Ser super(59) to Glu super(59) mimics Ser super(59) phosphorylation, and upon CD4 crosslinking, this mutant p56 super(lck) induces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56 super(lck). Mutant and wild-type p56 super(lck) have similar affinities for CD4 and similar kinase activities. In glutathione S-transferase fusion proteins, the p56 super(lck) Src homology 2 (SH2) domain with the SH3 domain and the unique N-terminal region (including Ser super(59)) has a different binding specificity for phosphotyrosyl proteins than the SH2 domain alone. Either deletion of the unique N-terminal region or mutation of Ser super(59) to Glu super(59) in the fusion protein reverts the phosphotyrosyl protein binding specificity back to that of the SH2 domain alone. These results suggest that phosphorylation of Ser super(59) regulates the function of p56 super(lck) by controlling binding specificity of its SH2 domain.