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First published online May 24, 2006
doi: 10.1242/10.1242/jcs.02946

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Caveolin-1 is required for signaling and membrane targeting of EphB1 receptor tyrosine kinase

Meri M. Vihanto¹, Cecile Vindis^1,*, Valentin Djonov², Douglas P. Cerretti³ and Uyen Huynh-Do^1,

¹ Department of Nephrology and Hypertension, and Department of Clinical Research, Inselspital, University of Bern, CH-3010 Bern, Switzerland
² Institute of Anatomy, University of Bern, CH-3000 Bern, Switzerland
³ Amgen Corporation, 1201 Amgen Court West, Seattle, WA 98101, USA

Author for correspondence (e-mail: uyen.huynh-do{at}insel.ch)

Accepted 17 February 2006

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.

Key words: Caveolae, Caveolin-1, Eph receptors, Ephrins, Signaling, Targeting

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