Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac


Autoria(s): Pollitt, Alice Y.; Grygielska, Beata; Leblond, Bertrand; Désiré, Laurent; Eble, Johannes A.; Watson, Steve P.
Data(s)

08/04/2010

Resumo

The C-type lectin-like receptor 2 (CLEC-2) activates platelets through Src and Syk tyrosine kinases via a single cytoplasmic YxxL motif known as a hem immunoreceptor tyrosine-based activation motif (hemITAM). Here, we demonstrate using sucrose gradient ultracentrifugation and methyl-beta-cyclodextrin treatment that CLEC-2 translocates to lipid rafts upon ligand engagement and that translocation is essential for hemITAM phosphorylation and signal initiation. HemITAM phosphorylation, but not translocation, is also critically dependent on actin polymerization, Rac1 activation, and release of ADP and thromboxane A(2) (TxA(2)). The role of ADP and TxA(2) in mediating phosphorylation is dependent on ligand engagement and rac activation but is independent of platelet aggregation. In contrast, tyrosine phosphorylation of the GPVI-FcRgamma-chain ITAM, which has 2 YxxL motifs, is independent of actin polymerization and secondary mediators. These results reveal a unique series of proximal events in CLEC-2 phosphorylation involving actin polymerization, secondary mediators, and Rac activation.

Formato

text

Identificador

http://centaur.reading.ac.uk/44800/1/Phosphorylation%20of%20CLEC-2%20is%20dependent%20on%20lipid%20rafts%2C%20actin%20polymerization%2C%20secondary%20mediators%20and%20Rac.pdf

Pollitt, A. Y. <http://centaur.reading.ac.uk/view/creators/90006835.html>, Grygielska, B., Leblond, B., Désiré, L., Eble, J. A. and Watson, S. P. (2010) Phosphorylation of CLEC-2 is dependent on lipid rafts, actin polymerization, secondary mediators, and Rac. Blood, 115 (14). pp. 2938-2946. ISSN 0006-4971 doi: 10.1182/blood-2009-12-257212 <http://dx.doi.org/10.1182/blood-2009-12-257212>

Idioma(s)

en

Publicador

American Society of Hematology

Relação

http://centaur.reading.ac.uk/44800/

creatorInternal Pollitt, Alice Y.

10.1182/blood-2009-12-257212

Tipo

Article

PeerReviewed