EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis
EPHB4 is necessary for LV valve specification, continued valve development postspecification, and valve maintenance. LV valve specification requires physical interaction between EPHB4 and RASA1 to limit activation of the Ras-MAPK pathway in lymphatic endothelial cells. Specifically, EPHB4-RASA1 physical interaction is necessary to dampen Ras-MAPK activation induced through the PIEZO1 oscillatory shear stress sensor. These findings reveal the mechanism by which EPHB4 and RASA1 regulate the development of LV valves.
Authors
- Philip E. Lapinski
- Eva M. Sevick‐Muraca (ORCID: https://orcid.org/0000-0002-8152-4847)
- Philip D. King (ORCID: https://orcid.org/0000-0002-5598-2748)
- Michael J. Davis (ORCID: https://orcid.org/0000-0002-3970-2208)
- Di Chen (ORCID: https://orcid.org/0000-0001-9509-2814)
- David K. Wiggins
- Yixin Tang (ORCID: https://orcid.org/0000-0002-5534-8907)
Institutions
- University of Michigan (US)
- Brown Foundation (US)
- University of Missouri (US)
Publication Details
- Journal
- Circulation Research
- Published
- 2024-10-18
- DOI
- https://doi.org/10.1161/circresaha.124.325383
- Citations
- 11
- Primary Topic
- Hippo pathway signaling and YAP/TAZ
- Type
- article
- Field-Weighted Citation Impact
- 3.59
Funders
- Yale University
- University of Michigan
- Oklahoma Medical Research Foundation
- Uppsala Universitet
- National Institutes of Health