What question did this study set out to answer?

To determine the molecular mechanism mediating the endocytosis and proteolytic down-regulation of activated VEGFR-1/Flt-1.

March 4, 2004The FASEB Journal

The c‐Cbl/CD2AP complex regulates VEGF‐induced endocytosis and degradation of Flt‐1 (VEGFR‐1)

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Authors

SKSatsuki KobayashiSapporo Toho Hospital ASAsako Sakaue-SawanoRIKEN Center for Brain Science YNYoshihisa NojimaKanazawa University

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Implication

In vitro study reveals that the c-Cbl/CD2AP complex drives VEGF-induced Flt-1 endocytosis and degradation in cell models, highlighting mechanisms governing angiogenesis signaling.

Key Points

To determine the molecular mechanism mediating the endocytosis and proteolytic down-regulation of activated VEGFR-1/Flt-1.
Examined protein-protein interactions and endocytic vesicle colocalization of Flt-1, c-Cbl, and CD2AP in a transient expression system with and without the VEGFR kinase inhibitor SU5416.
Assessed VEGF-induced Flt-1 internalization and ubiquitination in Flt-1-overexpressing NIH3T3 cells transfected with wild-type or mutated variants of CD2AP, c-Cbl, and Flt-1 (Y1333F).
VEGF stimulation prompted ternary complex formation and endosomal colocalization of Flt-1, c-Cbl, and CD2AP, which was blocked by SU5416, the Flt-1 Y1333F mutation, or dominant-negative CD2AP.
Wild-type CD2AP expression promoted VEGF-dependent Flt-1 ubiquitination and internalization, whereas mutant forms of CD2AP or c-Cbl completely failed to facilitate receptor down-regulation.

Cite This Study

Kobayashi et al. (2004) studied this question.

synapsesocial.com/papers/6a7ba0d6c2a640f0bcdf792a https://doi.org/10.1096/fj.03-0767fje

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Implication

In vitro study reveals that the c-Cbl/CD2AP complex drives VEGF-induced Flt-1 endocytosis and degradation in cell models, highlighting mechanisms governing angiogenesis signaling.

The c‐Cbl/CD2AP complex regulates VEGF‐induced endocytosis and degradation of Flt‐1 (VEGFR‐1)

Discussion

Member takes

Implication

Key Points

Cite This Study

The c‐Cbl/CD2AP complex regulates VEGF‐induced endocytosis and degradation of Flt‐1 (VEGFR‐1)

Discussion

Member takes

Implication

Key Points

Cite This Study

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