Disease relevance of Gp5

• Contrary to expectations, GP V -/- platelets were normal in size and expressed normal amounts of GP Ib-IX that was functional in von Willebrand factor binding, explaining why defects in GP V have not been observed in Bernard-Soulier syndrome, a bleeding disorder caused by a lack of functional GP Ib-IX-V [1].
• Absence of GP V also compromises thrombus stability [2].

High impact information on Gp5

• Thrombosis was generated in GP V null mice only in response to catalytically inactive thrombin, whereas thrombosis occurred in both genotypes (wild type and GP V null) in response to active thrombin [3].
• Previous analysis of platelets from GP V-null mice suggested a role for GP V as a negative modulator of platelet activation by thrombin [3].
• Because proteolytically inactive thrombin can activate wild-type mouse and human platelets after treatment with thrombin to cleave GP V, this mechanism is involved in thrombin-induced platelet aggregation [3].
• Consistent with these findings, GP V -/- mice had a shorter bleeding time [1].
• MAbs against GPIb-IX, GPV, CD31, and linear epitopes on GPIIIa had mild and transient effects on platelet counts and induced no spontaneous bleeding [4].

Biological context of Gp5

• These data support a role for GP V as a negative modulator of platelet activation [1].
• A role for glycoprotein (GP)V in platelet function has been proposed on the basis of observations that GP V is the major thrombin substrate on intact platelets cleaved during thrombin-induced platelet aggregation, and that GP V promotes GP Ib-IX surface expression in heterologous cells [1].
• Fifteen leucine-rich tandem repeats were present and the consensus sequence of the repeats was completely matched with that of human GPV [5].
• MATERIALS AND METHODS: The promotor activity of a -481/+22 5'-fragment of the mouse GPV gene was examined in normal mouse bone marrow cells (BMC) and various human cell lines using two distinct reporter gene assay systems, luciferase and green fluorescence protein (GFP) [6].

Anatomical context of Gp5

• Our study extends previous results and reports that electron microscopy of bone marrow from the GPV knockout mice revealed a normal MK ultrastructure and development of the demarcation membrane system (DMS) [7].
• Ultrastructural analysis of megakaryocytes in GPV knockout mice [7].
• 1C2 reacted with NIH-3T3 cells in which recombinant mouse or rat GPV was expressed [8].

Associations of Gp5 with chemical compounds

• The observation that collagen does not behave like CRP in platelets expressing reduced levels of GPVI, even in the combined presence of blocking antibodies against integrin alpha2beta1 and GPV, suggests that collagen has a greater affinity than CRP for GPVI, and/or that other receptors are involved in its binding to platelets [9].
• The chimeric pGMokPV encoded the NH2 part of GMok and the COOH part of GPV [10].

Analytical, diagnostic and therapeutic context of Gp5

• The role of GPV, also absent in BSS, was recently addressed by gene targeting in mice [7].
• In Northern blot, murine GPV mRNA was specifically expressed in murine platelets, bone marrow cells and megakaryocytic cell lines [5].

References