Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain

The many faces of Src: multiple functions of a prototypical tyrosine kinase

“…One of the de®ning mutations in all versions of v-src is the truncation and replacement of sequences encoding the COOH terminus so that Y527 is deleted (Parsons and Weber, 1989). The ®nding that either dephosphorylation or mutation of Y527 constitutively activates the c-Src kinase and enables it to transform cells, helped implicate this residue as a key regulatory element (Cartwright et al, 1987;Courtneidge, 1985;Kmiecik and Shalloway, 1987). Evidence suggests that, when phosphorylated, this tyrosine interacts intramolecularly with Src's own SH2 domain, thereby inactivating the kinase.…”

Activation of Src in human breast tumor cell lines: elevated levels of phosphotyrosine phosphatase activity that preferentially recognizes the Src carboxy terminal negative regulatory tyrosine 530

“…As the activity of Src is regulated to a large extent by phosphorylation and dephosphorylation of the COOHterminal negative regulatory Tyr 530 site Cartwright et al, 1987;Kmiecik and Shalloway, 1987;Tanaka et al, 1990), and as Src appeared to be less active when immunoprecipitated from cells grown in the presence of phosphatase inhibitors (Figure 1), we hypothesized that the tumor cell lines might contain a phosphatase activity that could speci®cally dephosphorylate Src at the tyrosine 530 regulatory site, thus having the potential to activate the enzyme. As a preliminary approach, we compared the ability of extracts from normal breast epithelial and HFF cells to extracts from the four breast tumor cell lines to dephosphorylate in vitro a Src family member Fyncarboxy terminal peptide (FCP) (residues 503 ± 537), which closely resembles the Src carboxy terminus around the tyrosine 530 site (O'Connor et al, 1995).…”

Rapid activation of sodium–proton exchange and extracellular signal-regulated protein kinase in fibroblasts by G protein-coupled 5-HT1A receptor involves distinct signalling cascades

“…DN-SHPT1D, a mutant phosphotyrosine phosphatase type 1D which incorporates a carboxy terminal deletion of 60 amino acids required for its tyrosine phosphorylation, was from Dr. Ben Neel (Beth Israel Hospital) [40]. Wild-type Src, dominant negative Src (K298MSrc) [41] and constitutively activated Src (Src Y527F) which lacks a key inhibitory phosphorylation site [42] were from Dr. L. Luttrell (Duke University).…”

“…Genistein, a broad-spectrum tyrosine kinase inhibitor, markedly attenuated the ability of 5-HT to activate ERK and NHE, whereas the structurally similar but inactive compound, daidzein, had no effect, supporting the involvement of tyrosine kinase(s) in both pathways (Table 1). PTP1D is a cytosolic phosphotyrosine phosphatase which has been shown to be a critical positive regulator of tyrosine kinase signals (DNA synthesis and ERK activation) initiated by both growth factor and G proteincoupled receptors [38][39][40][41][42][43][44][45][46][47][48][49]. Transfection of a cDNA construct encoding a mutant inactive PTP1D (∆PTP1D) molecule effectively blocked 5-HT-stimulated ERK, but had no effect on NHE activity.…”