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Regulatory role of dynamin‐2 in VEGFR‐2/KDR‐mediated endothelial signaling
Author(s) -
Bhattacharya Resham,
KangDecker Ningling,
Hughes Deborah A.,
Mukherjee Priyabrata,
Shah Vijay,
McNiven Mark A.,
Mukhopadhyay Debabrata
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-3889fje
Subject(s) - dynamin , microbiology and biotechnology , endosome , endocytosis , rab , vascular permeability , kinase insert domain receptor , angiogenesis , endocytic cycle , biology , signal transduction , tyrosine kinase , chemistry , receptor tyrosine kinase , vascular endothelial growth factor , vascular endothelial growth factor a , gtpase , cancer research , receptor , endocrinology , biochemistry , intracellular , vegf receptors
Vascular endothelial growth factor receptor‐2 (VEGFR‐2, also known as KDR) is a receptor tyrosine kinase (RTK) regulating mitogenic, chemotactic, permeability, and survival signals in vascular endothelial cells (EC) in response to its ligand, vascular permeability factor/VEGF (VPF/VEGF), arguably the most important angiogenic cytokine. However, the compartmentalization of KDR in EC and the mechanisms regulating this process have not been well defined. Here, we demonstrate that KDR is present on the plasma membrane, on endosomes, and in the perinuclear region of EC and colocalizes with early endosomal antigen (EEA1), caveolin‐1, and dynamin‐2, a signal transducing GTPase involved in receptor endocytosis. Furthermore, we also observed that dynamin‐2 coimmunoprecipitates with KDR and is required for EC signaling/survival. Interestingly, EC overexpressing a mutant form of dynamin deficient in GTP binding (K44A) caused a selective inhibition in KDR protein level and endosomal vesicle formation and induced cell cycle arrest by inducing p21. Taken together, our findings suggest that dynamin‐2 regulates KDR expression and function and hence plays an important role in VPF/VEGF mediated angiogenesis.