Lysophosphatidic Acid Modulates the Regenerative Responses of Human Gingival Fibroblasts and Enhances the Actions of Platelet-Derived Growth Factor

2004 ◽  
Vol 75 (2) ◽  
pp. 297-305 ◽  
Author(s):  
D. Roselyn Cerutis ◽  
Andrew Dreyer ◽  
Franco Cordini ◽  
Timothy P. McVaney ◽  
John S. Mattson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Human Gingival Fibroblasts ◽  
Platelet Derived Growth Factor ◽  
Gingival Fibroblasts

Activation of the small GTP-binding proteins rho and rac by growth factor receptors

1995 ◽  
Vol 108 (1) ◽  
pp. 225-233 ◽  
Author(s):  
C.D. Nobes ◽  
P. Hawkins ◽  
L. Stephens ◽  
A. Hall
Keyword(s):  
Plasma Membrane ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Phorbol Ester ◽  
Lysophosphatidic Acid ◽  
Actin Polymerization ◽  
Binding Proteins ◽  
Platelet Derived Growth Factor ◽  
Gtp Binding ◽  
Rho Protein

The small GTP-binding proteins, rho and rac, control signal transduction pathways that link growth factor receptors to the activation of actin polymerization. In Swiss 3T3 cells, rho proteins mediate the lysophosphatidic acid and bombesin-induced formation of focal adhesions and actin stress fibres, whilst rac proteins are required for the platelet-derived growth factor-, insulin-, bombesin- and phorbol ester (phorbol 12-myristate 13-acetate)-stimulated actin polymerization at the plasma membrane that results in membrane ruffling. To investigate the role of p85/p110 phosphatidylinositol 3-kinase in the rho and rac signalling pathways, we have used a potent inhibitor of this activity, wortmannin. Wortmannin has no effect on focal adhesion or actin stress fibre formation induced by lysophosphatidic acid, bombesin or microinjected recombinant rho protein. In contrast, it totally inhibits plasma membrane edge-ruffling induced by platelet-derived growth factor and insulin though not by bombesin, phorbol ester or microinjected recombinant rac protein. We conclude that phosphatidylinositol 3,4,5 trisphosphate mediates activation of rac by the platelet-derived growth factor and insulin receptors. The effects of lysophosphatidic acid on the Swiss 3T3 actin cytoskeleton can be blocked by the tyrosine kinase inhibitor, tyrphostin. Since tyrphostin does not inhibit the effects of microinjected rho protein, we conclude that lysophosphatidic acid activation of rho is mediated by a tyrosine kinase.

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