TAILIEUCHUNG - Báo cáo khoa học: Differential membrane compartmentalization of Ret by PTB-adaptor engagement

Glial cell line-derived neurotrophic factor family ligands act through the receptor tyrosine kinase Ret, which plays important roles during embryonic development for cell differentiation, survival, and migration. Ret signaling is markedly affected by compartmentalization of receptor complexes into membrane subdomains. | ỊFEBS Journal Differential membrane compartmentalization of Ret by PTB-adaptor engagement T. K. Lundgren Moritz Luebke Anna Stenqvist and Patrik Ernfors Division of Molecular Neurobiology Department of MedicalBiochemistry and Biophysics Karolinska Institute Stockholm Sweden Keywords fractionation Frs2 lipid rafts PTB adaptors Ret Correspondence P. Ernfors Division of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Karolinska Institute 171 77 Stockholm Sweden Fax 468 341960 Tel 468 52487659 E-mail Received 14 December 2007 revised 23 February 2008 accepted 26 February 2008 doi Glial cell line-derived neurotrophic factor family ligands act through the receptor tyrosine kinase Ret which plays important roles during embryonic development for cell differentiation survival and migration. Ret signaling is markedly affected by compartmentalization of receptor complexes into membrane subdomains. Ret can propagate biochemical signaling from within concentrates in cholesterol-rich membrane microdomains or lipid rafts or outside such regions but the mechanisms for and consequences of Ret translocation between these membrane compartments remain largely unclear. Here we investigate the interaction of Shc and Frs2 phosphotyrosine-binding domain-containing adaptor molecules with Ret and their function in redistributing Ret to specialized membrane compartments. We found that engagement of Ret with the Frs2 adaptor results in an enrichment of Ret in lipid rafts and that signal transduction pathways and chemotaxis responses depend on the integrity of such rafts. The competing Shc adaptor did not promote Ret translocation to equivalent domains and Shc-mediated effects were less affected by disruption of lipid rafts. However by expressing a chimeric Shc protein that localizes to lipid rafts we showed that biochemical signaling downstream of Ret resembled that of Ret signaling via Frs2. We have identified a .

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