An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.

Platelet activation is regulated by both positive and negative signals. G6B-b is an inhibitory platelet receptor with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). The molecular basis of inhibition by G6B-b is currently unknown but...

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Autores principales:	Carmen H Coxon, Amanda J Sadler, Jiandong Huo, R Duncan Campbell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/122682a0ac8d4d3d948250224b15ce21
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spelling	oai:doaj.org-article:122682a0ac8d4d3d948250224b15ce212021-11-18T08:08:17ZAn investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.1932-620310.1371/journal.pone.0049543https://doaj.org/article/122682a0ac8d4d3d948250224b15ce212012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23185356/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Platelet activation is regulated by both positive and negative signals. G6B-b is an inhibitory platelet receptor with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). The molecular basis of inhibition by G6B-b is currently unknown but thought to involve the SH2 domain-containing tyrosine phosphatase SHP-1. Here we show that G6B-b also associates with SHP-2, as well as SHP-1, in human platelets. Using a number of biochemical approaches, we found these interactions to be direct and that the tandem SH2 domains of SHP-2 demonstrated a binding affinity for G6B-b 100-fold higher than that of SHP-1. It was also observed that while SHP-1 has an absolute requirement for phosphorylation at both motifs to bind, SHP-2 can associate with G6B-b when only one motif is phosphorylated, with the N-terminal SH2 domain and the ITIM being most important for the interaction. A number of other previously unreported SH2 domain-containing proteins, including Syk and PLCγ2, also demonstrated specificity for G6B-b phosphomotifs and may serve to explain the observation that G6B-b remains inhibitory in the absence of both SHP-1 and SHP-2. In addition, the presence of dual phosphorylated G6B-b in washed human platelets can reduce the EC(50) for both CRP and collagen.Carmen H CoxonAmanda J SadlerJiandong HuoR Duncan CampbellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49543 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carmen H Coxon Amanda J Sadler Jiandong Huo R Duncan Campbell An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.
description	Platelet activation is regulated by both positive and negative signals. G6B-b is an inhibitory platelet receptor with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). The molecular basis of inhibition by G6B-b is currently unknown but thought to involve the SH2 domain-containing tyrosine phosphatase SHP-1. Here we show that G6B-b also associates with SHP-2, as well as SHP-1, in human platelets. Using a number of biochemical approaches, we found these interactions to be direct and that the tandem SH2 domains of SHP-2 demonstrated a binding affinity for G6B-b 100-fold higher than that of SHP-1. It was also observed that while SHP-1 has an absolute requirement for phosphorylation at both motifs to bind, SHP-2 can associate with G6B-b when only one motif is phosphorylated, with the N-terminal SH2 domain and the ITIM being most important for the interaction. A number of other previously unreported SH2 domain-containing proteins, including Syk and PLCγ2, also demonstrated specificity for G6B-b phosphomotifs and may serve to explain the observation that G6B-b remains inhibitory in the absence of both SHP-1 and SHP-2. In addition, the presence of dual phosphorylated G6B-b in washed human platelets can reduce the EC(50) for both CRP and collagen.
format	article
author	Carmen H Coxon Amanda J Sadler Jiandong Huo R Duncan Campbell
author_facet	Carmen H Coxon Amanda J Sadler Jiandong Huo R Duncan Campbell
author_sort	Carmen H Coxon
title	An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.
title_short	An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.
title_full	An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.
title_fullStr	An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.
title_full_unstemmed	An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.
title_sort	investigation of hierachical protein recruitment to the inhibitory platelet receptor, g6b-b.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/122682a0ac8d4d3d948250224b15ce21
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An investigation of hierachical protein recruitment to the inhibitory platelet receptor, G6B-b.

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