The Sema domain, a protein interacting module, of MET and RON receptor tyrosine kinases
This family includes MET and RON receptor tyrosine kinases. MET is encoded by the c-met protooncogene. MET is the receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF and MET regulates multiple cellular events and are essential for the development of several tissues and organs, including the placenta, liver, and several groups of skeletal muscles. RON receptor tyrosine kinase is a Macrophage-stimulating protein (MSP) receptor. Upon binding of MSP, RON is activated via autophosphorylation within its kinase catalytic domain, resulting in a variety of effects including proliferation, tubular morphogenesis, angiogenesis, cellular motility and invasiveness. By interacting with downstream signaling molecules, it regulates macrophage migration, phagocytosis, and nitric oxide production. MET and RON receptors have been implicated in cancer development and migration. They are composed of alpha-beta heterodimers. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a Sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic tyrosine kinase domain. The Sema domain is necessary for receptor dimerization and activation.
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