title: Syk protein tyrosine kinase involves PECAM-1 signaling through tandem immunotyrosine inhibitory motifs in human THP-1 macrophages.
abstract: 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.
authors: Department of Surgery and Pathology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New District, Shanghai, PR China.
authors: Junchen
authors: J
authors: Wang
authors: Yanling
authors: Y
authors: Wu
authors: Hai
authors: H
authors: Hu
authors: Weimin
authors: W
authors: Wang
authors: Ying
authors: Y
authors: Lu
authors: Huiming
authors: H
authors: Mao
authors: Xiaoqing
authors: X
authors: Liu
authors: Zhongmin
authors: Z
authors: Liu
authors: Bing-guan
authors: BG
authors: Chen
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D019000:Phosphotyrosine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000072377:Syk Kinase; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases