Multiple endocytic pathways of G protein- coupled receptors delineated by GIT1 sensitivity.
Recently, we identified a GTPase-activating protein for the ADP ribosylation factor family of small GTP- binding proteins that we call GIT1. This protein initially was identified as an interacting partner for the G protein-coupled receptor kinases, and its overexpression was found to affect signaling and internalization of the prototypical beta(2)-adrenergic receptor. Here, we report that GIT1 overexpression regulates internalization of numerous, but not all, G protein-coupled receptors. The specificity of the GIT1 effect is not related to the type of G protein to which a receptor couples, but rather to the endocytic route it uses. GIT1 only affects the function of G protein- coupled receptors that are internalized through the clathrin-coated pit pathway in a beta-arrestin- and dynamin-sensitive manner. Furthermore, the GIT1 effect is not limited to G protein-coupled receptors because overexpression of this protein also affects internalization of the epidermal growth factor receptor. However, constitutive agonist-independent internalization is not regulated by GIT1, because transferrin uptake is not affected by GIT1 overexpression. Thus, GIT1 is a protein involved in regulating the function of signaling receptors internalized through the clathrin pathway and can be used as a diagnostic tool for defining the endocytic pathway of a receptor.[1]References
- Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Claing, A., Perry, S.J., Achiriloaie, M., Walker, J.K., Albanesi, J.P., Lefkowitz, R.J., Premont, R.T. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
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