title: EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains.
abstract: Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with "reverse" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.
authors: Developmental Biology Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
authors: K
authors: K
authors: Brückner
authors: J
authors: J
authors: Pablo Labrador
authors: P
authors: P
authors: Scheiffele
authors: A
authors: A
authors: Herb
authors: P H
authors: PH
authors: Seeburg
authors: R
authors: R
authors: Klein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D036387:Ephrin-B1; D017353:Gene Deletion; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009928:Organ Specificity; D019606:Phosphoamino Acids / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D036387:Ephrin-B1; C491309:Grip1 protein, mouse; C491308:Grip1 protein, rat; C485567:Grip2 protein, mouse; C118486:Grip2 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019606:Phosphoamino Acids; D017346:Protein Serine-Threonine Kinases