Platelet-derived growth factor activation of mitogen-activated protein kinase depends on the sequential activation of phosphatidylcholine-specific phospholipase C, protein kinase C-zeta and Raf-1.
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-zeta (PKC-zeta). Both PC-PLC and PKC-zeta 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-zeta co-immunoprecipitates with, phoshorylates and activates Raf-1, suggesting that in the PDGF- and PC-PLC-activated MAPK pathway, PKC-zeta operates in a signalling complex as a direct activator of Raf-1.
van Dijk
M C
MC
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Hilkmann
H
H
van Blitterswijk
W J
WJ
D000818:Animals; D001409:Bacillus cereus / Q000201:enzymology; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000242:Cyclic AMP; D004815:Epidermal Growth Factor; D007211:Indoles; D019950:Mitogen-Activated Protein Kinase 1; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf; D011993:Recombinant Fusion Proteins; D010738:Type C Phospholipases; D000099221:Protein Kinase C zeta; C105598:phosphatidylcholine-specific phospholipase C; C064758:Ro 31-8220