Modification of Ser59 in the unique N-terminal region of tyrosine kinase p56lck regulates specificity of its Src homology 2 domain

During T-cell activation, Ser59 in the unique N-terminal region of p56lck is phosphorylated. Mutation of Ser59 to Glu59 mimics Ser59 phosphorylation, and upon CD4 crosslinking, this mutant p56lck induces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56l...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1995-06, Vol.92 (13), p.5778-5782
Main Authors: Joung, I, Kim, T, Stolz, L A, Payne, G, Winkler, D G, Walsh, C T, Strominger, J L, Shin, J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biochemistry
Glutamic Acid
Glutathione Transferase - biosynthesis
HeLa Cells
Humans
Kinetics
Lymphocyte Activation
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Models, Structural
Molecular Sequence Data
Mutagenesis, Site-Directed
Oncogene Proteins, Viral - metabolism
Phosphopeptides - chemistry
Phosphopeptides - isolation & purification
Phosphorylation
Point Mutation
Protein-Tyrosine Kinases - biosynthesis
Protein-Tyrosine Kinases - chemistry
Protein-Tyrosine Kinases - metabolism
Proteins
Recombinant Fusion Proteins - biosynthesis
Recombinant Proteins - biosynthesis
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
Serine
Substrate Specificity
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
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Description
Summary:During T-cell activation, Ser59 in the unique N-terminal region of p56lck is phosphorylated. Mutation of Ser59 to Glu59 mimics Ser59 phosphorylation, and upon CD4 crosslinking, this mutant p56lck induces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56lck. Mutant and wild-type p56lck have similar affinities for CD4 and similar kinase activities. In glutathione S-transferase fusion proteins, the p56lck Src 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 Ser59 to Glu59 in the fusion protein reverts the phosphotyrosyl protein binding specificity back to that of the SH2 domain alone. These results suggest that phosphorylation of Ser59 regulates the function of p56lck by controlling binding specificity of its SH2 domain.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.92.13.5778