scholarly journals Involvement of Phosphatidylcholine-specific Phospholipase C in Platelet-derived Growth Factor-induced Activation of the Mitogen-activated Protein Kinase Pathway in Rat-1 Fibroblasts

1997 ◽  
Vol 272 (17) ◽  
pp. 11011-11016 ◽  
Author(s):  
Marc C. M. van Dijk ◽  
Francisco J. G. Muriana ◽  
John de Widt ◽  
Henk Hilkmann ◽  
Wim J. van Blitterswijk
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Mitogen Activated Protein Kinase ◽  
Platelet Derived Growth Factor ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals 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

1997 ◽  
Vol 325 (2) ◽  
pp. 303-307 ◽  
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.

scholarly journals Phosphorylation sites at the C-terminus of the platelet-derived growth factor receptor bind phospholipase C gamma 1.

1993 ◽  
Vol 4 (1) ◽  
pp. 49-57 ◽  
Author(s):  
A Kashishian ◽  
J A Cooper
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Growth Factor Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Platelet Derived Growth Factor ◽  
Phosphorylation Sites ◽  
C Terminus ◽  
Mitogen Activated Protein ◽  
Src Homology

We have identified two tyrosine phosphorylation sites, Tyr 1009 and Tyr 1021, in the C-terminal noncatalytic region of the human platelet-derived growth factor (PDGF) receptor beta subunit. Mutant receptors with phenylalanine substitutions at either or both of these tyrosines were expressed in dog epithelial cells. Mutation of Tyr 1021 markedly reduced the PDGF-stimulated binding of phospholipase C (PLC) gamma 1 but had no effect on binding of the GTPase activator protein of Ras or of phosphatidylinositol 3 kinase. Mutation of Tyr 1009 reduced binding of PLC gamma 1 less severely. Mutation of Tyr 1021, or both Tyr 1009 and Tyr 1021, also reduced the PDGF-dependent binding of a transiently expressed fusion protein containing the two Src-homology 2 domains from PLC gamma 1. Mutation of Tyr 1021, or both Tyr 1009 and Tyr 1021, greatly reduced PDGF-stimulated tyrosine phosphorylation of PLC gamma 1 but did not prevent the tyrosine phosphorylation of other cell proteins, including mitogen-activated protein kinase. We conclude that Tyr 1021, and possibly Tyr 1009, is a binding site for PLC gamma 1.

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