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

Journal Article · Wed Mar 15 04:00:00 EST 1989 · J. Biol. Chem.; (United States)

OSTI ID:6101957

Bryckaert, M C; Rendu, F; Tobelem, G; Wasteson, A

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.

• Research Organization: Institut National de la Sante et de la Recherche Medicale U 150, Paris (France)
• OSTI ID: 6101957
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 264:8; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION
BLOOD PLATELETS
BODY FLUIDS
CHEMICAL REACTIONS
COLLAGEN
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MATERIALS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHOPROTEINS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SCLEROPROTEINS
TIME DEPENDENCE
TRACER TECHNIQUES