PMID- 16723736 OWN - NLM STAT- MEDLINE DCOM- 20070112 LR - 20191210 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 119 IP - Pt 11 DP - 2006 Jun 1 TI - Caveolin-1 is required for signaling and membrane targeting of EphB1 receptor tyrosine kinase. PG - 2299-309 AB - Eph receptor tyrosine kinases are key players during the development of the embryonic vasculature; however, their role and regulation in adult angiogenesis remain to be defined. Caveolae are flask-shaped invaginations of the cell membrane; their major structural protein, caveolin-1, has been shown to regulate signaling molecules localized in these micro-domains. The interaction of caveolin-1 with several of these proteins is mediated by the binding of its scaffolding domain to a region containing hydrophobic amino acids within these proteins. The presence of such a motif within the EphB1 kinase domain prompted us to investigate the caveolar localization and regulation of EphB1 by caveolin-1. We report that EphB1 receptors are localized in caveolae, and directly interact with caveolin-1 upon ligand stimulation. This interaction, as well as EphB1-mediated activation of extracellular-signal-regulated kinase (ERK), was abrogated by overexpression of a caveolin-1 mutant lacking a functional scaffolding domain. Interaction between Ephs and caveolin-1 is not restricted to the B-subclass of receptors, since we show that EphA2 also interacts with caveolin-1. Furthermore, we demonstrate that the caveolin-binding motif within the kinase domain of EphB1 is primordial for its correct membrane targeting. Taken together, our findings establish caveolin-1 as an important regulator of downstream signaling and membrane targeting of EphB1. FAU - Vihanto, Meri M AU - Vihanto MM AD - Department of Nephrology and Hypertension, Inselspital, University of Bern, Switzerland. FAU - Vindis, Cecile AU - Vindis C FAU - Djonov, Valentin AU - Djonov V FAU - Cerretti, Douglas P AU - Cerretti DP FAU - Huynh-Do, Uyen AU - Huynh-Do U LA - eng PT - Journal Article PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (Caveolin 1) RN - 0 (Ephrin-B2) RN - 97C5T2UQ7J (Cholesterol) RN - EC 2.7.10.1 (Receptor, EphA2) RN - EC 2.7.10.1 (Receptor, EphB1) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - CHO Cells MH - COS Cells MH - Caveolin 1/drug effects/genetics/*metabolism MH - Cell Line, Tumor MH - Cell Membrane/*metabolism MH - Chlorocebus aethiops MH - Cholesterol/pharmacology MH - Cricetinae MH - Ephrin-B2/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism MH - Humans MH - Phosphorylation MH - Protein Transport/physiology MH - Receptor, EphA2/metabolism MH - Receptor, EphB1/*metabolism MH - Signal Transduction/*physiology EDAT- 2006/05/26 09:00 MHDA- 2007/01/16 09:00 CRDT- 2006/05/26 09:00 PHST- 2006/05/26 09:00 [pubmed] PHST- 2007/01/16 09:00 [medline] PHST- 2006/05/26 09:00 [entrez] AID - 119/11/2299 [pii] AID - 10.1242/jcs.02946 [doi] PST - ppublish SO - J Cell Sci. 2006 Jun 1;119(Pt 11):2299-309. doi: 10.1242/jcs.02946.