Phosphatidic acid modulates DNA synthesis, phospholipase C, and platelet-derived growth factor mRNAs in cultured mesangial cells. Role of protein kinase C.

This study examines the role of protein kinase C (PKC) in platelet-derived growth factor (PDGF)-induced vascular smooth muscle (VSM) cell proliferation and initial signaling events. A 24-h pretreatment of VSM cells with 200 nM phorbol 12-myristate 13-acetate (PMA) completely abolished immunologically reactive PKC activity. Depletion of PKC activity from VSM cells did not attenuate PDGF-stimulated [3H]thymidine incorporation compared with control cells. Similarly, acute activation of PKC by treatment with 200 nM PMA for 10 min had no effect on PDGF-mediated [3H]thymidine incorporation. Both PMA and PDGF increased c-fos induction to the same magnitude; however, treatment with PMA did not induce DNA synthesis in these cells. In PKC-depleted cells PDGF-mediated c-fos induction was reduced by 50-60%, while DNA synthesis in response to PDGF stimulation was not reduced. PKC depletion did not alter PDGF-stimulated increase in cytosolic calcium levels, 125I-PDGF binding, or receptor autophosphorylation. On the basis of these results, we conclude that PKC activation and c-fos induction do not play a significant role in PDGF-mediated mitogenesis in VSM cells.

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Role of Protein Kinase C on the Expression of Platelet-Derived Growth Factor and Endothelin-1 in the Retina of Diabetic Rats and Cultured Retinal Capillary Pericytes

Diabetes ◽

10.2337/diabetes.52.3.838 ◽

2003 ◽

Vol 52 (3) ◽

pp. 838-845 ◽

Cited By ~ 82

Author(s):

T. Yokota ◽

R. C. Ma ◽

J.-Y. Park ◽

K. Isshiki ◽

K. B. Sotiropoulos ◽

...

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Diabetic Rats ◽

Platelet Derived Growth Factor ◽

Endothelin 1 ◽

Kinase C ◽

Retinal Capillary

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Platelet-derived growth factor activation of mitogen-activated protein kinase depends on the sequential activation of phosphatidylcholine-specific phospholipase C, protein kinase C-ζ and Raf-1

Biochemical Journal ◽

10.1042/bj3250303 ◽

1997 ◽

Vol 325 (2) ◽

pp. 303-307 ◽

Cited By ~ 50

Author(s):

Marc C. M. VAN DIJK ◽

Henk HILKMANN ◽

Wim J. VAN BLITTERSWIJK

Keyword(s):

Protein Kinase C ◽

Growth Factor ◽

Protein Kinase ◽

Phospholipase C ◽

Mapk Pathway ◽

Mitogen Activated Protein Kinase ◽

Platelet Derived Growth Factor ◽

Kinase C ◽

Mitogen Activated Protein ◽

Pkc Ζ

The mechanism of Raf-1 activation by platelet-derived growth factor (PDGF) is poorly defined. We previously reported that, in Rat-1 fibroblasts, PDGF activates a phosphatidylcholine-specific phospholipase C (PC-PLC) and that the product, diacylglycerol, somehow activates protein kinase C-ζ (PKC-ζ). Both PC-PLC and PKC-ζ activities were required for PDGF activation of mitogen-activated protein kinase (MAPK). Now we report that MAPK activation by exogenous PC-PLC depends on Raf-1 activation. PKC-ζ co-immunoprecipitates with, phoshorylates and activates Raf-1, suggesting that in the PDGF- and PC-PLC-activated MAPK pathway, PKC-ζ operates in a signalling complex as a direct activator of Raf-1.

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