Claudin-like Protein 24 Interacts with the VEGFR-2 and VEGFR-3 Pathways and Regulates Lymphatic Vessel Development

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2010 May 5

PMID 20439428

Citations 20

Authors

Pipsa Saharinen

Hanna Helotera

Juho Miettinen

Camilla Norrmen

Gabriela DAmico

Michael Jeltsch

Tobias Langenberg

Wouter Vandevelde

Annelii Ny

Mieke Dewerchin

Peter Carmeliet

Kari Alitalo

Affiliations

Soon will be listed here.

Abstract

The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that clp24 knockdown in Danio rerio and Xenopus laevis results in defective lymphatic development. Targeted disruption of Clp24 in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the Clp24(-/-) phenotype was further aggravated in the Vegfr2(+/LacZ) or Vegfr3(+/LacZ) backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.

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