Summary
The immunoreceptor tyrosine-based activatory motif (ITAM) containing glycoprotein, GPVI, plays an important signalling role in platelet activation. GPVI binds to exposed collagen fibres at the site of vascular damage and the ensuing signalling events contribute to formation of a thrombus to repair the damaged area. The control of this activatory signalling pathway by immunoreceptor tyrosine-based inhibitory motif (ITIM) containing molecules is beginning to be understood in the platelet. Two such ITIM molecules are known in platelets. CD31 is expressed on human and mouse platelets, whilst PIR-B is expressed only on murine platelets. CD31 associates with the cytoplasmic phosphatases SHP-1 and SHP-2 and is phosphorylated upon platelet activation by collagen, thrombin and FcγRIIA cross-linking. Mice deficient in CD31 show enhanced responses to GPVI agonists, demonstrating that CD31 is a negative regulator of platelet-collagen responses. PIR-B has recently been shown to be expressed on murine platelets and megakaryocytes. PIR-B is constitutively phosphorylated in murine platelets and associates with unidentified tyrosine phosphorylated proteins of 80, 73 and 38 kDa upon activation by thrombin or GPVI. In megakaryocytes, there is minimal phosphorylation of PIR-B under basal or activated conditons. No functional inhibitory response for PIR-B has been identified in platelets and no phosphatases have been associated with this molecule in platelets. The role for inhibitory receptor systems in platelets to control collagen-induced activation is still in its infancy and further work in this field is rapidly progressing.
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Snell, D.C., Pasquet, JM., Watson, S.P. (2001). ITIM-bearing receptors in platelets. In: Cooper, M.D., Takai, T., Ravetch, J.V. (eds) Activating and Inhibitory Immunoglobulin-like Receptors. Springer, Tokyo. https://doi.org/10.1007/978-4-431-53940-7_9
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DOI: https://doi.org/10.1007/978-4-431-53940-7_9
Publisher Name: Springer, Tokyo
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