The protooncogene c-Cbl has recently emerged as an E3 ubiquitin ligase for activated receptor tyrosine kinases. We report here that c-Cbl also mediates the ubiquitination of another protooncogene, the non-receptor tyrosine kinase c-Src, as well as of itself. The c-Cbl-dependent ubiquitination of Src and c-Cbl requires c-Cbl's RING finger, Src kinase activity, and c-Cbl's tyrosine phosphorylatio...

STAT3 is a member of a family of transcription factors with Src homology 2 (SH2) domains that are activated by tyrosine phosphorylation in response to a wide variety of cytokines and growth factors. In this study, we investigated the mechanism of STAT3 activation by the Src family of nonreceptor tyrosine kinases, which have been linked to STAT activation in both normal and transformed cell type...

Src family tyrosine kinases participate in the regulation of cell adhesion, cell growth and differentiation. Here, we examine for the first time the potential role of Src for growth regulation of human pancreatic carcinoma cells. By immunohistochemical analysis, Src was overexpressed in 13/13 pancreatic carcinoma tissue but not in 6 normal pancreatic tissue specimen. In Western blots of total c...

Activation of the tyrosine kinase of a temperature-sensitive mutant v-Src oncoprotein in quiescent Rat-1 cells leads to passage through the cell cycle. Temperature shift experiments show that v-Src is needed to leave G0, to pass a relatively stable G1 "pause" point, and to pass a later G1 point committing cells to S phase. Classic immediate early responses that activate both AP-1 DNA binding an...

The product of the viral src gene (v-src) is the protein tyrosine kinase pp60v-src. Among the known consequences of pp60v-src activity is the reduction in permeability of gap junctions, an effect that is counteracted by the calcium antagonist TMB-8 (8-N,N-[diethylamino]octyl-3,4,5-trimethoxybenzoate). We show here that a decrease in intracellular pH (pHi) also counteracts the v-src effect: junc...

The non-receptor tyrosine kinase Src is recruited to activated fibroblast growth factor receptor (FGFR) complexes through the adaptor protein factor receptor substrate 2 (FRS2). Here, we show that Src kinase activity has a crucial role in the regulation of FGFR1 signalling dynamics. Following receptor activation by ligand binding, activated Src is colocalized with activated FGFR1 at the plasma ...

Src functions depend on its association with the plasma membrane and with specific membrane-associated assemblies. Many aspects of these interactions are unclear. We investigated the functions of kinase, SH2, and SH3 domains in Src membrane interactions. We used FRAP beam-size analysis in live cells expressing a series of c-Src-GFP proteins with targeted mutations in specific domains together w...

The function of the nonreceptor tyrosine kinase c-Src as a plasma membrane-associated molecular effector of a variety of extracellular stimuli is well known. Here, we show that c-Src is also present within mitochondria, where it phosphorylates cytochrome c oxidase (Cox). Deleting the c-src gene reduces Cox activity, and this inhibitory effect is restored by expressing exogenous c-Src. Furthermo...

c-Src is a tightly regulated non-receptor tyrosine kinase. We describe the C-terminus of c-Src as a ligand for a PDZ (postsynaptic density 95, PSD-95; discs large, Dlg; zonula occludens-1, ZO-1) domain. The C-terminal residue Leu of c-Src is essential for binding to a PDZ domain. Mutation of this residue does not affect the intrinsic kinase activity in vitro, but interferes with c-Src regulatio...

Objective: Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43—a transmembrane protein constituting gap junctions—is involved pathology. However, the role Cx43 smooth muscle (SPCs) remained unclear. Approach Results: Human SPCs cultured from CD34 + peripheral blood mononuclear expressed cell markers, such as MHC (myosin hea...