Signal regulation by family conspiracy.
The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two subgroups: SIRP alpha and SIRP beta, containing more than ten members. SIRP alpha has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors. This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRP alpha may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRP beta subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP). DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRP beta to activating machinery. SIRP alpha and SIRP beta thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus.
Max-Planck-Institut für Biochemie, Department of Molecular Biology, Martinsried, Germany.
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Ullrich
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011971:Receptors, Immunologic; D015398:Signal Transduction; D018909:src Homology Domains
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D011971:Receptors, Immunologic; D020794:Receptor Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases