Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular mechanisms that mediate mitogenic effects of gastrin remain largely unknown. The present studies were designed to examine if protein tyrosine kinases (PTKs) mediate growth effects of gastrin on a rat intestinal epithelial cell line (IEC-6 cells). Gastrin (< 10 nM) was mitogenic for IEC-6 cells. PTK activity of cell membranes was stimulated in response to 0.01-10.0 nM and 0.05-10.0 microM gastrin in a double biphasic manner. Cells labeled with H3(32)PO4 were stimulated with gastrin and cellular proteins immunoprecipitated with phosphotyrosine antibodies. Endogenous proteins were phosphorylated in a dose- (100% effective dose = 0.1-1.0 nM) and time-dependent manner; at > 10 nM gastrin, the second peak of response was not measured in intact cells. Thus the growth and phosphorylation response of intact cells to gastrin was similar. Both high [dissociation constant (Kd) = 1 nM]- and low (Kd = approximately 0.1 microM)-affinity gastrin binding sites are present on IEC-6 cells. The results of the present study suggest that occupancy of both high- and low-affinity gastrin-binding sites can potentially activate membrane-associated PTKs. However, in intact cells, occupancy of low-affinity sites apparently attenuates kinase activity resulting in reduced protein phosphorylation. Eight protein bands [with relative molecular weight (M(r)) of 32-145 kDa] were tyrosine phosphorylated in intact cells in response to 0.1-1.0 nM gastrin, including two pp60 src-like proteins (with M(r) of 54 and 62 kDa). Thus the growth response pattern of a target cell to gastrin may depend on the stimulation of kinases and other factors (phosphatases?) that phosphorylate and/or dephosphorylate several proteins including c-src-like proteins in a dose-dependent manner.
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PMID:Phosphorylation of pp62 and pp54 src-like proteins in a rat intestinal cell line in response to gastrin. 807 24

Stimulation of small cell lung cancer (SCLC) cells with neuropeptides bombesin, bradykinin, gastrin, and neurotensin resulted in increased tyrosine kinase activity and tyrosine phosphorylation of a number of polypeptides including a p120 kDa polypeptide identified by immunoblotting as focal adhesion kinase (p125FAK). The neuropeptides stimulated a rapid, concentration-dependent phosphorylation of p125FAK (EC50 of 1 nM, 5 nM, and 2 nM for bombesin, bradykinin, and gastrin, respectively), which was receptor mediated and inhibited by both specific and broad-spectrum neuropeptide receptor antagonists. Specific inhibition of protein tyrosine kinase activity by tyrphostin-25 inhibited both basal and neuropeptide-stimulated SCLC cell growth. These results identify a novel neuropeptide-stimulated growth signaling event in SCLC cells.
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PMID:Neuropeptides stimulate tyrosine phosphorylation and tyrosine kinase activity in small cell lung cancer cell lines. 880 78

Bombesin-like peptides, including the mammalian homologue gastrin-releasing peptides, are highly expressed and secreted by neuroendocrine cells in prostate carcinoma (PCa) tissues and are likely to be related to the progression of this disease. In the present study, we show that bombesin enhances the migration of androgen-independent PCa cells (PC-3) in vitro, while not affecting their adhesion to extracellular matrix proteins. The bombesin-increased motility of PC-3 cells occurs through its receptor, and, as shown with inhibitors, it likely requires activation of both protein tyrosine kinases (PTKs) and protein kinases C (PKCs). Because the focal adhesion kinase pp125FAK plays a key role in adhesion/motility and is highly expressed in advanced PCa, we examined whether in PC-3 cells bombesin signal transduction triggers the tyrosine phosphorylation of this PTK and of associated integrins and signaling proteins likely to be present in focal adhesion plaques. pp125FAK tyrosine phosphorylation was stimulated by bombesin and mimicked by PKC activation with the tumor-promotor phorbol 12-myristate-13-acetate (PMA). Moreover, this effect of bombesin on pp125FAK tyrosine phosphorylation requires the presence of both active PKC and cytoskeleton integrity since this signal was abolished by down-regulating PKCs induced by prolonged PMA treatment or by PKC inhibition with GF 109203X, as well as by disruption of the cytoskeleton with cytochalasin D. We also show that bombesin increases the tyrosine phosphorylation of a 95-kDa protein (pp95) which was co-immunoprecipitated with the alpha v and beta (3 and 5) subunits, forming integrin receptors with alpha v in PC-3 cells. The protein pp95 is distinct from the endogenously tyrosine-phosphorylated beta3 subunit. In addition, upon bombesin treatment, the beta1, beta3 and beta5 integrin subunits co-immunoprecipitated with pp125FAK and major phosphotyrosine (pY)-containing proteins of 125 and 68-70 kDa, likely corresponding to pp125FAK and paxillin. Together our data suggest that, in addition to PKC activation, tyrosine phosphorylation of pp125FAK and integrin-associated proteins may play an important role in bombesin signaling, triggering the processes of PCa cell motility and invasion.
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PMID:Bombesin stimulates the motility of human prostate-carcinoma cells through tyrosine phosphorylation of focal adhesion kinase and of integrin-associated proteins. 924 95