Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell Activation

摘要: According to a recently proposed hypothesis, initiation of signal transduction via immunoreceptors depends on interactions the engaged immunoreceptor with glycosphingolipid-enriched membrane microdomains (GEMs). In this study, we describe novel GEM-associated transmembrane adaptor protein, termed phosphoprotein associated GEMs (PAG). PAG comprises short extracellular domain 16 amino acids and 397-amino acid cytoplasmic tail containing ten tyrosine residues that are likely phosphorylated by Src family kinases. lymphoid cell lines in resting peripheral blood α/β T cells, is expressed as constitutively tyrosine-phosphorylated protein binds major negative regulator kinases, kinase Csk. After activation becomes rapidly dephosphorylated dissociates from Expression COS cells results recruitment endogenous Csk, altered activity, impaired phosphorylation Src-specific substrates. Moreover, overexpression Jurkat downregulates receptor–mediated transcription factor nuclear activated cells. These findings collectively suggest absence external stimuli, PAG–Csk complex transmits regulatory signals thus may help keep quiescent state.