Tracing the evolution and function of the Trk superfamily of receptor tyrosine kinases.
Most growth factors and their receptors have been strongly conserved during evolution. In contrast, Trks (Tropomyosin-related kinases) and related receptors in the Trk superfamily, Rors (receptor tyrosine kinase-like orphan receptors), Musks (muscle specific kinases) and Ddrs (discoidin domain receptor family), appear to be ancient, but their function has been lost in multiple lineages and the roles for the receptors have been modified over time. We will trace the evolution of the Trk superfamily and discuss possible conserved functional roles, including a unifying theme of target recognition by growing axons. We present an analogy between the evolution of G-protein-coupled receptors and receptor tyrosine kinases (RTKs), proposing that an important driving force for the divergence of receptors is the ease of divergence of their ligands.
Sossin
Wayne S
WS
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. wayne.sossin@mcgill.ca
D000818:Animals; D000070818:Discoidin Domain Receptors; D019143:Evolution, Molecular; D008024:Ligands; D011494:Protein Kinases / Q000235:genetics; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D011975:Receptors, Mitogen / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011975:Receptors, Mitogen; D017475:Receptors, Nerve Growth Factor; D011494:Protein Kinases; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; C041311:tropomyosin kinase