Pertussis toxin-sensitive activation of p21ras by G protein-coupled receptor agonists in fibroblasts.
AUTOR(ES)
van Corven, E J
RESUMO
Some agonists of G protein-coupled receptors, such as thrombin and lysophosphatidic acid (LPA), can promote cell proliferation via a pertussis toxin (PTX)-sensitive signaling pathway. While these agonists stimulate phospholipase C and inhibit adenylate cyclase, it appears that other, as-yet-unidentified, effector pathways are required for mitogenesis. Here we report that LPA and a thrombin receptor agonist peptide rapidly activate the protooncogene product p21ras in quiescent fibroblasts. This activation is inhibited by PTX and yet not attributable to known PTX-sensitive G protein pathways, including stimulation of phospholipases, inhibition of adenylate cyclase, or modulation of ion channels. LPA- and peptide-induced p21ras activation is inhibited by the tyrosine kinase inhibitor genistein, at doses that do not affect epidermal growth factor-induced p21ras activation. Thus, a heterotrimeric G protein of the Gi subfamily regulates activation of p21ras by LPA and thrombin, possibly through an intermediary tyrosine kinase. This pathway may critically participate in mitogenic signaling downstream from certain G protein-coupled receptors.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=45851Documentos Relacionados
- Coupling of a purified goldfish brain kainate receptor with a pertussis toxin-sensitive G protein.
- Activation of the muscarinic K+ channel by P2-purinoceptors via pertussis toxin-sensitive G proteins in guinea-pig atrial cells.
- Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein.
- Evidence for pseudomonas exotoxin A receptors on plasma membrane of toxin-sensitive lm fibroblasts.
- Pertussis toxin-sensitive G proteins are transported toward synaptic terminals by fast axonal transport.