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Title: Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation

Abstract

Platelet-derived growth factor (PDGF) is known to inhibit collagen-induced platelet aggregation. Collagen-induced binding of /sup 125/I-PDGF to human washed platelets was therefore investigated. It was found to be time-dependent, reaching a plateau at 20 degrees C after 30 min, collagen concentration-dependent, specifically inhibited by unlabeled PDGF, and saturable. Scatchard plot analysis showed a single class of sites with 3000 +/- 450 molecules bound/cell and an apparent KD of 1.2 +/- 0.2 10(-8) M. The effects of PDGF on collagen-induced phosphoinositide breakdown and protein phosphorylation were also investigated. At 50 ng/ml PDGF, a concentration which completely inhibited collagen-induced aggregation, the breakdown of (/sup 32/P)phosphatidylinositol 4,5-biphosphate (PIP2) and (/sup 32/P)phosphatidylinositol 4-phosphate (PIP) was observed, but the subsequent replenishment of (/sup 32/P)PIP2 was inhibited. The same PDGF concentration totally inhibited collagen-induced phosphatidic acid formation. PDGF also completely prevented phosphorylation of P43 and P20, as a result of protein kinase C activation consecutive to phosphoinositide metabolism. These results suggest that a specific PDGF receptor can be induced by collagen, and PDGF can effect the early events of collagen-induced platelet activation by inhibiting PIP2 resynthesis and P43 and P20 phosphorylation. It is concluded that PDGF might be involved in a negative feed-back control of plateletmore » activation.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Institut National de la Sante et de la Recherche Medicale U 150, Paris (France)
OSTI Identifier:
6101957
Resource Type:
Journal Article
Journal Name:
J. Biol. Chem.; (United States)
Additional Journal Information:
Journal Volume: 264:8
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BLOOD PLATELETS; BLOOD COAGULATION; COLLAGEN; BIOCHEMICAL REACTION KINETICS; GROWTH FACTORS; PHOSPHORYLATION; INHIBITION; IODINE 125; PHOSPHOPROTEINS; PHOSPHORUS 32; RECEPTORS; TIME DEPENDENCE; TRACER TECHNIQUES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CHEMICAL REACTIONS; DAYS LIVING RADIOISOTOPES; ELECTRON CAPTURE RADIOISOTOPES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KINETICS; LIGHT NUCLEI; MATERIALS; MEMBRANE PROTEINS; MITOGENS; NUCLEI; ODD-EVEN NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; PHOSPHORUS ISOTOPES; PROTEINS; RADIOISOTOPES; REACTION KINETICS; SCLEROPROTEINS; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Bryckaert, M C, Rendu, F, Tobelem, G, and Wasteson, A. Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation. United States: N. p., 1989. Web.
Bryckaert, M C, Rendu, F, Tobelem, G, & Wasteson, A. Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation. United States.
Bryckaert, M C, Rendu, F, Tobelem, G, and Wasteson, A. 1989. "Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation". United States.
@article{osti_6101957,
title = {Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation},
author = {Bryckaert, M C and Rendu, F and Tobelem, G and Wasteson, A},
abstractNote = {Platelet-derived growth factor (PDGF) is known to inhibit collagen-induced platelet aggregation. Collagen-induced binding of /sup 125/I-PDGF to human washed platelets was therefore investigated. It was found to be time-dependent, reaching a plateau at 20 degrees C after 30 min, collagen concentration-dependent, specifically inhibited by unlabeled PDGF, and saturable. Scatchard plot analysis showed a single class of sites with 3000 +/- 450 molecules bound/cell and an apparent KD of 1.2 +/- 0.2 10(-8) M. The effects of PDGF on collagen-induced phosphoinositide breakdown and protein phosphorylation were also investigated. At 50 ng/ml PDGF, a concentration which completely inhibited collagen-induced aggregation, the breakdown of (/sup 32/P)phosphatidylinositol 4,5-biphosphate (PIP2) and (/sup 32/P)phosphatidylinositol 4-phosphate (PIP) was observed, but the subsequent replenishment of (/sup 32/P)PIP2 was inhibited. The same PDGF concentration totally inhibited collagen-induced phosphatidic acid formation. PDGF also completely prevented phosphorylation of P43 and P20, as a result of protein kinase C activation consecutive to phosphoinositide metabolism. These results suggest that a specific PDGF receptor can be induced by collagen, and PDGF can effect the early events of collagen-induced platelet activation by inhibiting PIP2 resynthesis and P43 and P20 phosphorylation. It is concluded that PDGF might be involved in a negative feed-back control of platelet activation.},
doi = {},
url = {https://www.osti.gov/biblio/6101957}, journal = {J. Biol. Chem.; (United States)},
number = ,
volume = 264:8,
place = {United States},
year = {Wed Mar 15 00:00:00 EST 1989},
month = {Wed Mar 15 00:00:00 EST 1989}
}