CLONING AND CHARACTERIZATION OF LNK, A SIGNAL-TRANSDUCTION PROTEIN THAT LINKS T-CELL RECEPTOR ACTIVATION SIGNAL TO PHOSPHOLIPASE C-GAMMA(1), GRB2, AND PHOSPHATIDYLINOSITOL 3-KINASE

A cDNA encoding a signal transduction protein with a Src homology 2 (SH2) domain and a tyrosine phosphorylation site mas cloned from a rat lymph node cDNA library, This protein, which we designate Lnk, has a calculated molecular weight of 33,988. When T lymphocytes were activated by antibody-mediated crosslinking of the T-cell receptor and CD4, Lnk became tyrosine phosphorylated, In activated T lymphocytes, phospholipase C gamma(1), phosphatidylinositol 3-kinase, and Grb-2 coimmunoprecipitated with Lnk. Our results suggest that Lnk becomes tyrosine phosphorylated and links the immediate tyrosine phosphorylation signals of the TCR to the distal phosphatidylinositol 3-kinase, phospholipase C gamma(1) and Ras signaling pathways through its multifunctional tyrosine phosphorylation site.