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

Vihanto, Meri M; Vindis, Cecile; Djonov, Valentin; Cerretti, Douglas P; Huynh-Do, Uyen (2006). Caveolin-1 is required for signaling and membrane targeting of EphB1 receptor tyrosine kinase. Journal of cell science, 119(Pt 11), pp. 2299-309. Cambridge: Company of Biologists Limited 10.1242/jcs.02946

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
UniBE Contributor:	Djonov, Valentin Georgiev, Huynh-Do, Uyen
Subjects:	600 Technology > 610 Medicine & health
ISSN:	0021-9533
ISBN:	16723736
Publisher:	Company of Biologists Limited
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1242/jcs.02946
PubMed ID:	16723736
Web of Science ID:	000238413300013
URI:	https://boris.unibe.ch/id/eprint/18937 (FactScience: 1208)