Signals elicited from human platelets by synthetic, triple helical, collagen-like peptides.
Synthetic collagen-like peptides, of general structure [Gly-Pro-HyP]n, adopt the triple-helical structure which is essential for the platelet-reactivity of native collagens. These peptides are potent activators of platelets, stimulating platelet aggregation at much lower dose than collagen fibres, but, unlike collagen fibres, they are not recognised by the integrin alpha 2 beta 1. We have examined the ability of the synthetic peptides to activate the various signalling pathways which regulate human platelet function. The peptides are potent activators of Ca2+ mobilisation and of protein kinase C, and they stimulate tyrosine phosphorylation of some substrates preferentially. However, in contrast with native type I collagen fibres, they are unable to inhibit platelet adenylate cyclase. This suggests a mode of action for the synthetic peptides which substantially overlaps, but which is not entirely identical with, that of native collagen.
Achison
M
M
Department of Biochemistry, University of Cambridge, UK.
Joel
C
C
Hargreaves
P G
PG
Sage
S O
SO
Barnes
M J
MJ
Farndale
R W
RW
D001081:Apyrase / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000138:chemical synthesis / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005998:Glycine; D006801:Humans; D006909:Hydroxyproline; D010750:Phosphoproteins; D010766:Phosphorylation / Q000187:drug effects; D011108:Polymers / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D001798:Blood Proteins; D010750:Phosphoproteins; D011108:Polymers; C039077:platelet protein P47; D003094:Collagen; D001081:Apyrase; D006909:Hydroxyproline; D002118:Calcium; D005998:Glycine