EphB1 interaction with caveolin-1 in endothelial cells modulates caveolae biogenesis

Chinnaswamy Tiruppathi, Sushil C. Regmi, Dong Mei Wang, Gary C.H. Mo, Peter T. Toth, Stephen M. Vogel, Radu V. Stan, Mark Henkemeyer, Richard D. Minshall, Jalees Rehman, Asrar B. Malik

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Caveolae, the cave-like structures abundant in endothelial cells (ECs), are important for multiple signaling processes such as production of nitric oxide and caveolae-mediated intracellular trafficking. Using superresolution microscopy, fluorescence resonance energy transfer, and biochemical analysis, we observed that the EphB1 receptor tyrosine kinase constitutively interacts with caveolin-1 (Cav-1), the key structural protein of caveolae. Activation of EphB1 with its ligand Ephrin B1 induced EphB1 phosphorylation and the uncoupling EphB1 from Cav-1 and thereby promoted phosphorylation of Cav-1 by Src. Deletion of Cav-1 scaffold domain binding (CSD) motif in EphB1 prevented EphB1 binding to Cav-1 as well as Srcdependent Cav-1 phosphorylation, indicating the importance of CSD in the interaction. We also observed that Cav-1 protein expression and caveolae numbers were markedly reduced in ECs from EphB1-deficient (EphB1-/-) mice. The loss of EphB1 binding to Cav-1 promoted Cav-1 ubiquitination and degradation, and hence the loss of Cav-1 was responsible for reducing the caveolae numbers. These studies identify the crucial role of EphB1/Cav-1 interaction in the biogenesis of caveolae and in coordinating the signaling function of Cav-1 in ECs.

Original languageEnglish (US)
Pages (from-to)1167-1182
Number of pages16
JournalMolecular biology of the cell
Issue number11
StatePublished - May 2020

ASJC Scopus subject areas

  • Medicine(all)


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