Monomeric (glycine-proline-hydroxyproline)(10) repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI

We have previously reported that a triple-helical, collagen-related peptide (CRP; also known as CRP-XL) containing a glycine-proline-hydroxyproline (G PP*) repeat motif and cross-linked through cysteine residues at its N-termi nus and C-terminus is a powerful stimulus of platelet aggregation and secre tion through the surface receptor glycoprotein VI (GPVI). The activation of platelets is associated with tyrosine phosphorylation of the tyrosine kina se Syk and phospholipase C gamma 2 (PLC gamma 2). We now report that the no n-cross-linked backbone of CRP, monomeric CRP (mCRP), stimulates the tyrosi ne phosphorylation of Syk and PLC gamma 2 in platelets and induces the weak secretion of [H-3]5-hydroxytryptamine ([H-3]5-HT) and aggregation. The act ion of mCRP does not seem to be due to spontaneous cross-linking, because a lkylation of the cysteine residues leads to an increase in activity. The tr ipeptide backbone of CRP, GPP(10)(*) (in which P* represents hydroxyproline ) also stimulates platelet shape change and the weak tyrosine phosphorylati on of Syk and PLC gamma 2, but is unable to induce aggregation or secretion . The monomeric peptides partly inhibit the release of [H-3]S-HT by CRP, su ggesting that they are partial agonists of the collagen receptor GPVI. Thes e results demonstrate that GPP* present as a repeat motif is sufficient to activate the platelet collagen receptor GPVI but that the cross-linking of monomers brings about an increase in activity.