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

• Published in: Journal of cell science Vol. 119; no. Pt 11; pp. 2299 - 2309
• Main Authors: Vihanto, Meri M, Vindis, Cecile, Djonov, Valentin, Cerretti, Douglas P, Huynh-Do, Uyen
• Format: Journal Article
• Language: English
• Published: England 01.06.2006
• Subjects: Animals; Caveolin 1 - drug effects; Caveolin 1 - genetics; Caveolin 1 - metabolism; Cell Line, Tumor; Cell Membrane - metabolism; Cercopithecus aethiops; CHO Cells; Cholesterol - pharmacology; COS Cells; Cricetinae; Ephrin-B2 - pharmacology; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - metabolism; Humans; Phosphorylation; Protein Transport - physiology; Receptor, EphA2 - metabolism; Receptor, EphB1 - metabolism; Signal Transduction - physiology
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.02946

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.