Syk protein tyrosine kinase involves PECAM-1 signaling through tandem immunotyrosine inhibitory motifs in human THP-1 macrophages.

Autor: Wang J; Department of Surgery and Pathology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New District, Shanghai, PR China., Wu Y, Hu H, Wang W, Lu Y, Mao H, Liu X, Liu Z, Chen BG
Jazyk: angličtina
Zdroj: Cellular immunology [Cell Immunol] 2011; Vol. 272 (1), pp. 39-44. Date of Electronic Publication: 2011 Sep 29.
DOI: 10.1016/j.cellimm.2011.09.009
Abstrakt: Although recent evidence supports a functional relationship between platelet endothelial cell adhesion molecule (PECAM-1) and Syk tyrosine kinase, little is known about the interaction of Syk with PECAM-1. We report that down-regulation of Syk inhibits the spreading of human THP-1 macrophage cells. Moreover, our data indicate that Syk binds PECAM-1 through its immune tyrosine-based inhibitory motif (ITIM), and dual phosphorylation of the ITIM domain of PECAM-1 leads to activation of Syk. Our results indicate that the distance between the phosphotyrosines could be up to 22 amino acids in length, depending on the conformational flexibility, and that the dual ITIM tyrosine motifs of PECAM-1 facilitate immunoreceptor tyrosine-based activation motif-like signaling. The preferential binding of PECAM-1 to Src homology region 2 domain-containing phosphatase-2 or Syk may depend on their relative affinities, and could provide a mechanism by which signal transduction from PECAM-1 is internally regulated by both positive and negative signaling enzymes.
(Copyright © 2011 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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