KIF13B-mediated VEGFR2 trafficking is essential for vascular leakage and metastasis in vivo.

ABSTRACT: VEGF-A induces vascular leakage and angiogenesis via activating the cell surface localized receptor VEGF receptor 2 (VEGFR2). The amount of available VEGFR2 at the cell surface is however tightly regulated by trafficking of VEGFR2 by kinesin family 13 B (KIF13B), a plus-end kinesin motor, to the plasma membrane of endothelial cells (ECs). Competitive inhibition of interaction between VEGFR2 and KIF13B by a peptide kinesin-derived angiogenesis inhibitor (KAI) prevented pathological angiogenesis in models of cancer and eye disease associated with defective angiogenesis. Here, we show the protective effects of KAI in VEGF-A-induced vascular leakage and cancer metastasis. Using an EC-specific KIF13B knockout (Kif13biECKO ) mouse model, we demonstrated the function of EC expressed KIF13B in med

SUBMITTER: Waters SB 

PROVIDER: S-EPMC8548263 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature