Platelet-derived growth factor stimulates phosphorylation of growth factor receptor-binding protein-2 in vascular smooth muscle cells.
Year: 1994
Type: article
Abstract: Growth factor receptor-binding protein-2 (GRB2) couples growth factor receptor activation to the p21ras nucleotide exchange factor son-of-sevenless (SOS). Son-of-sevenless can serve as a substrate for mitogen-activated protein kinases and may be subject to feed back regulation in mitogen-stimulated cells. Herein, we demonstrate phosphorylation on GRB2 in rat A10 vascular smooth muscle cells exposed to platelet-derived growth factor (PDGF). Lysates from smooth cells stimulated with PDGF revealed a shift in the electrophoretic mobility of GRB2. Further investigation confirmed that phosphorylation on GRB2 accompanied this mobility shift. Phosphorylation on GRB2 was time-dependent and correlated with PDGF receptor activation. The time-course for phosphorylation of GRB2 and subsequent decay corresponded with other events characteristic of platelet-derived growth factor signaling. GRB2 was not phosphorylated in cells treated with phorbol 12-myristate 13-acetate, and down-regulation of protein kinase C failed to attenuate phosphorylation on GRB2 in response to growth factor. Analysis of GRB2 immune complexes revealed a kinase activity capable of phosphorylating GRB2 in vitro and demonstrated that the kinase activated in response to PDGF may physically associate with GRB2 signaling complexes.
Source: Journal of Biological Chemistry
Authors: C W Benjamin, D A Linseman, D A Jones
Institution: Pfizer (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1507299757