Calcium-dependent increase in tyrosine kinase activity stimulated by angiotensin II.

Abstract

The cellular effects of numerous hormones and neurotransmitters, including the vasoactive agents angiotensin II (Angil) and [Args]vasopressin, are mediated in part by protein-serine/threonine kinases activated by increase of cytosolic Ca2+ concentration. In this study, we have tested the ability of Ca2+-mobilizing agents to activate cellular tyrosine kinases.Treatment of intact GN4 liver epithelial cells with Angl rapidly ('15 sec) increased tyrosine kinase activity measured either in unfractionated cell lysates or in anti-phosphotyrosine immune complexes from detergent-solubilized cells. Increased phosphorylation of the exogenous substrate poly(GlusiTyr2D) (3-to 4-fold over control) by immunoprecipitated kinases closely paralleled the time-and dose-dependence of the appearance of tyrosine phosphoproteins in intact cells. This effect of AnglI was mimicked by thapsigargin, a Ca2+-elevating tumor promoter. The ability of Angl, but not epidermal growth factor, to increase tyrosine kinase activity was blocked in cells loaded with the Ca2' chelator bis-(O-aminophenoxy)-ethane-NNN',N'-tetraacetic acid. Dephosphorylation of immunoprecipitated proteins by tyrosine phosphatase treatment was accompanied by a 60-70% loss in in vitro kinase activity, suggesting that the Angl-sensitive kinase(s) are activated by phosphorylation in intact cells. These findings demonstrate a link between two widely occurring signaling pathways, the tyrosine kinases and the Ca2+ secondmessenger system, and suggest the possible involvement of Ca2+-activated tyrosine kinases in the endocrine actions ofAngIl and [Argglvasopressin.

Reactive Oxygen Intermediates Mediate Angiotensin II-induced c-Jun•c-Fos Heterodimer DNA Binding Activity and Proliferative Hypertrophic Responses in Myogenic Cells

“…lipase C-␥1 (19,22,38). In cardiac fibroblasts, it has been shown that Ang-II induces tyrosine phosphorylation of the p125 focal adhesion kinase (p125 Fak ), a dominant tyrosine kinase substrate, after stimulation of many G-protein-coupled receptors and of p46…”

“…In different cell types a variety of second messengers have been involved in the transduction of Ang-II signaling. In cardiac myocytes and VSMCs Ang-II activates phospholipase C through a G-protein-coupled receptor, liberates inositol triphosphate; induces calcium release from inositol triphosphate-sensitive calcium storage sites; activates protein kinase C, phospholipase A 2 , phospholipase D, adenilate cyclase, and arachidonic acid metabolism; and stimulates the tyrosine kinases, c-Raf1, and mitogen-activated protein kinases cascade (12,(15)(16)(17)(18)(19)(20)(21)(22)(23). Interestingly, the activation of both phospholipase A 2 and phospholipase D stimulates the intracellular generation of ROIs through the formation of arachidonate and phosphatidic acid (PA), respectively.…”

Cholecystokinin-stimulated tyrosine phosphorylation of p125FAK and paxillin is mediated by phospholipase C-dependent and -independent mechanisms and requires the integrity of the actin cytoskeleton and participation of p21rho

“…Numerous studies have demonstrated that with CCK receptor activation [10][11][12][13][14]44,45], similar to the activation of a number of other G-protein-coupled receptors for neuropeptides that have no intrinsic tyrosine kinase activity, stimulation of tyrosine phosphorylation of a number of proteins occurs and is probably an important intracellular signalling cascade [18,[46][47][48]. Recent studies [8,18,49] suggest that with these neuropeptides, similar to the effect seen with oncogenes and integrins, the tyrosine phosphorylation of p125 FAK and the cytoskeletal protein paxillin may be particularly important in mediating numerous cellular effects, especially on growth.…”

Evidence for requirement of tyrosine phosphorylation in endothelial P2y‐ and P2u‐ purinoceptor stimulation of prostacyclin release

“…Force et al, 1991;Marrero et al, 1994;Chen et al, 1994;Duff et al, 1994). This tyrosine phosphorylation response is generally reported for G proteincoupled receptors which also activate phospholipase C (PLC), and has been considered as downstream of the consequent elevation in cystolic Ca2" and activation of protein kinase C (PKC) (Force et al, 1991;Huckle et al, 1992;Offermanns et al, 1993). Recently PLC-independent mechanisms have been proposed for the G protein activation of tyrosine kinases (e.g.…”