RGD Reference Report - Mer receptor tyrosine kinase signaling participates in platelet function. - Rat Genome Database

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Mer receptor tyrosine kinase signaling participates in platelet function.

Authors: Chen, C  Li, Q  Darrow, AL  Wang, Y  Derian, CK  Yang, J  De Garavilla, L  Andrade-Gordon, P  Damiano, BP 
Citation: Chen C, etal., Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1118-23. Epub 2004 May 6.
RGD ID: 1582496
Pubmed: (View Article at PubMed) PMID:15130911
DOI: Full-text: DOI:10.1161/01.ATV.0000130662.30537.08

OBJECTIVE: Recently, mice made deficient in growth arrest-specific gene 6 product (Gas6) or in which Gas6 gene expression was inhibited were shown to have platelet dysfunction and to be less susceptible to thrombosis. The aim of this study was to define and characterize the relevant Gas6 receptor or receptors involved in platelet function. METHODS AND RESULTS: Using RT-PCR and Western blot analysis we found that mer was the predominantly expressed subtype in mouse and human platelets, whereas axl and rse were not detected. We generated mer-deficient mice by targeted disruption of the mer receptor gene. Platelets derived from mer-deficient mice had decreased platelet aggregation in responses to low concentrations of collagen, U46619, and PAR4 thrombin receptor agonist peptide in vitro. However, the response to ADP was not different from wild-type platelets. Knockout of the mer gene protected mice from collagen/epinephrine-induced pulmonary thromoembolism and inhibited ferric chloride-induced thrombosis in vivo. Tail bleeding times, coagulation parameters, and peripheral blood cell counts in mer-deficient mice were similar to wild-type mice. CONCLUSIONS: Our data provide the first evidence that mer, presumably through activation by its ligand Gas6, participates in regulation of platelet function in vitro and platelet-dependent thrombosis in vivo.

Annotation

Disease Annotations    
pulmonary embolism  (IAGP,ISO)
thrombosis  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Mertk  (MER proto-oncogene, tyrosine kinase)

Genes (Mus musculus)
Mertk  (MER proto-oncogene tyrosine kinase)

Genes (Homo sapiens)
MERTK  (MER proto-oncogene, tyrosine kinase)


Additional Information