The role of protein kinase C in activation and termination of mitogen-activated protein kinase activity in angiotensin II-stimulated rat aortic smooth-muscle cells

Malarkey, Kevin; McLees, Angela; Paul, Andrew; Gould, Gwyn W.; Plevin, Robin

doi:10.1016/0898-6568(95)02036-5

Cited by 33 publications

(40 citation statements)

References 39 publications

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“…Recent reports also have implicated the novel PKCs-d and -e in the activation of Raf-1 and the MEK/ERK kinases downstream of Raf-1 (Cai et al, 1997;Cacace et al, 1996;Malarkey et al, 1996;Ueda et al, 1996). In COS-1 cells PKCd activates the MEK/ERK pathway in a Raf-1 dependent and Ras independent manner (Ueda et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase C-ε associates with the Raf-1 kinase and induces the production of growth factors that stimulate Raf-1 activity

et al. 1997

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Several observations indicate that the Raf-1 kinase is a downstream eector of protein kinase C-e (PKCe). We recently have shown that Raf-1 is constitutively activated in PKCe transformed Rat6 ®broblasts, and transformation can be reverted by expression of a dominant negative Raf-1, but not a dominant negative Ras mutant (Cacace et al., 1996). Cai et al. (1997) demonstrated that PKCe induced proliferation of NIH3T3 cells is independent of Ras or Src, but depends on Raf-1. These authors further suggested that PKCe activates Raf-1 by direct phosphorylation. Here we have investigated the functional interaction between PKCe and Raf-1. PKCe, but not PKCa, was found to bind to the Raf-1 kinase domain. The association appeared to be direct, as it could be reconstituted in vitro with puri®ed proteins. Raf-1 and PKCe could be co-precipitated from Sf-9 insect cells and PKCe transformed NIH313 cells (NIH/ e). The association was negatively regulated by ATP in vitro and by TPA treatment in NIH/e cells, but not in Sf-9 insect cells. Raf-1 was constitutively activated in NIH/e cells. However, using coexpression experiments in Sf-9 cells and transiently transfected A293 cells we did not obtain any evidence for a direct activation of Raf-1 by PKCe. PKCe did not induce translocation of Raf-1 to the membrane. Furthermore, PKCe did not activate Raf-1 nor enhance the kinase activity of Raf-1 that had been pre-activated by coexpression of Ras or the Lck tyrosine kinase. In contrast, conditioned media from PKCe transformed cells induced a robust activation of Raf-1. This activation could be partially reproduced by recombinant TGFb, a growth factors secreted by PKCe transformed Rat6 cells. In conclusion, our results suggest that PKCe stimulates Raf-1 indirectly by inducing the production of autocrine growth factors.

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Section: Introductionmentioning

confidence: 99%

Protein kinase C-ε associates with the Raf-1 kinase and induces the production of growth factors that stimulate Raf-1 activity

et al. 1997

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“…3). In RASMC, ERK1/2 is activated by PKC3 (Malarkey et al 1996) and by PKC z (Berra et al 1995), which lack the C2 domain, thus their kinase activities are Ca 2C independent (Liao et al 1997). It is relevant that PKCa is calcium activated (Toker 1998), though its interactions with ERK1/2 (Seo et al 2004), and indeed cell hypertrophy/proliferation remains unclear (Stewart & O'Brian 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms underlying AT1-mediated MAP kinase responses are related to amplification by PKCs (Malarkey et al 1996, Oro et al 2007. In myocytes, PKC isoenzymes are differentially activated by various stimuli (Clerk et al 1994, Puceat et al 1994, Strait & Samarel 2000 and PKCs differently regulate MAP kinase cascades in an isoenzymespecific and time-dependent manner (Heidkamp et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Through interactions with AT1-R and phospholipase C activation, Ang II triggers the inositol trisphosphate (IP 3 )/ calcium and the protein kinase C (PKC) signalling pathways (Malarkey et al 1996). Of the 12 distinct members of the PKC family (Mellor & Parker 1998), which all exhibit distinct properties and activation profiles (Mellor & Parker 1998), PKCa is the major Ca 2C -dependent phorbol-ester-sensitive PKC in neonatal rat ventricular myocytes (Puceat et al 1994) and after phosphorylation it has been shown to inhibit cell proliferation (Acs et al 1997).…”

Section: Introductionmentioning

confidence: 99%

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Changes in angiotensin II type 1 receptor signalling pathways evoked by a monoclonal antibody raised to the N-terminus

Xiao¹,

Puddefoot²,

Barker³

et al. 2008

Journal of Endocrinology

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The extracellular N-terminus of G-protein-coupled receptors may be involved in signalling events. We examined this in the angiotensin II type 1 receptor (AT1-R) using monoclonal antibody 6313/G2, raised against a conserved sequence in the N-terminal domain, and found it evokes inhibitory and stimulatory responses. In rat aortic smooth muscle cell (RASMC) primary cultures, 6313/G2 (2 . 5 mg/ml) inhibited both basal and angiotensin II (Ang II; 10]thymidine incorporation. Exposure to 6313/G2 gave sustained increases in phosphorylated protein kinase Ca (PKCa) but gave a decrease in phosphorylated p44/42 extracellular signal-regulated kinases (ERK1/2) sustained from 10 min to 48 h compared with untreated control RASMC.In contrast, Ang II had no effect on PKCa, and, though it is acutely stimulatory (up to 5 min), it had no sustained effect on ERK1/2 either. Using Fura-2 and microfluorimetry, 6313/G2 added alone induced a transient increase in intracellular calcium ([Ca 2C ] i ), with a characteristic response curve different from that of Ang II itself. The antibody was without effect on an Ang II-stimulated activator protein-1 reporter system, though it reduced unstimulated reporter activity. Such discriminatory effects on intracellular signalling suggest that the AT1-R N-terminus itself might be a target for therapeutic intervention in chronic vascular disease.

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“…Activation of PKC by AII has been reported to be required for AII-induced growth in several studies of cultured vascular smooth muscle cells. [84][85][86][87] Tyrosine phosphorylation: The potential role of tyrosine phosphorylation in AII-induced growth in cultured smooth muscle cells has attracted considerable interest recently (reviewed in reference 88). AII induces tyrosine phosphorylation of multiple proteins in cultured rat aortic vascular smooth muscle cells.…”

Section: Phospholipase C (Plc)mentioning

confidence: 99%

Molecular and cellular mechanisms of action of angiotensin II (AT1) receptors in vascular smooth muscle

Hughes

1998

J Hum Hypertens

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The role of protein kinase C in activation and termination of mitogen-activated protein kinase activity in angiotensin II-stimulated rat aortic smooth-muscle cells

Cited by 33 publications

References 39 publications

Protein kinase C-ε associates with the Raf-1 kinase and induces the production of growth factors that stimulate Raf-1 activity

Protein kinase C-ε associates with the Raf-1 kinase and induces the production of growth factors that stimulate Raf-1 activity

Changes in angiotensin II type 1 receptor signalling pathways evoked by a monoclonal antibody raised to the N-terminus

Molecular and cellular mechanisms of action of angiotensin II (AT1) receptors in vascular smooth muscle

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