The Src kinase family comprises nine homologous members whose distinct expression patterns and cellular distributions indicate that they have unique roles. These roles have not been determined because genetic manipulation has not produced clearly distinct phenotypes, and the kinases' homology complicates generation of specific inhibitors. Through insertion of a modified FK506 binding protein (i...

src kinase activity is elevated in some human tumors, including breast and colon cancers. The precise cellular function of the src family kinases is not clearly understood, but they appear to be involved in numerous signaling pathways. We studied the effects of PD173955, a novel src family-selective tyrosine kinase inhibitor, on cancer cell lines and found that it has significant antiproliferat...

The multisubstrate docking protein, growth-factor-receptor-bound protein 2-associated binder 1 (Gab1), which is phosphorylated on tyrosine residues following activation of receptor tyrosine kinases and cytokine receptors, regulates cell proliferation, survival and epithelial morphogenesis. Gab1 is also tyrosine phosphorylated following activation of G-protein-coupled receptors (GPCRs) where its...

The non–receptor protein tyrosine, Src, is a 60-kDa protein that is the archetypal member of a nine-gene family, including Src, Yes, Fyn, Lyn, Lck, Hck, Fgr, Blk, and Yrk, that plays a critical role in regulation of proliferation, differentiation, migration, adhesion, invasion, angiogenesis, and immune function (for detailed reviews, see refs. 1–4). All Src family kinases are myristoylated at t...

Src family tyrosine kinases mediate signal transduction cascades through two functional states. In its inactive state, the SH2 domain of c-Src binds to an intramolecular phosphotyrosine near the C terminus of the protein. In the cell, kinase activity can be switched on by dephosphorylation of the key tyrosine residue. Proteins, small molecules and synthetic phosphopeptides also can relieve kina...

Zinc is coreleased with glutamate from excitatory nerve terminals throughout the central nervous system and acutely inhibits N-methyl-d-aspartate (NMDA) receptor activation. Here we report that cultured murine cortical neurons briefly exposed to sublethal concentrations of zinc developed increased intracellular free Na(+), phosphorylation of Src kinase at tyrosine 220, and tyrosine phosphorylat...