Distinct binding patterns of HS1 to the Src SH2 and SH3 domains reflect possible mechanisms of recruitment and activation of downstream molecules.
We previously identified a gene, LckBP1, which encodes a protein that binds to the Lck SH3 domain and is identical to murine SH1. Using unstimulated T lymphocytes, we further demonstrated that Lck binds to HS1 in vivo and that HS1 is tyrosine phosphorylated upon TCR stimulation. In the present report, we analyzed the binding pattern of several src kinases and HS1 in greater detail. The Lck SH3 domain binds to HS1 constitutively, while the Lck SH2 domain associates with HS1 only upon TCR stimulation. A similar binding pattern was observed with Lyn and HS1, but not with Fyn and HS1, in which the Fyn SH2 region associates with HS1 upon TCR stimulation but the Fyn SH3 region does not associate with HS1 regardless of TCR stimulation. Such distinct binding patterns of the src kinase SH2 and SH3 domains to HS1 may represent a mechanism by which src family kinases select substrates and activate particular downstream signaling pathways.
Takemoto
Y
Y
Institute of Immunology, Syntex-Roche, Chiba, Japan.
Sato
M
M
Furuta
M
M
Hashimoto
Y
Y
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018909:src Homology Domains / Q000276:immunology*; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; C061909:HCLS1 protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases