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Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity.

Publication ,  Journal Article
Claing, A; Perry, SJ; Achiriloaie, M; Walker, JK; Albanesi, JP; Lefkowitz, RJ; Premont, RT
Published in: Proc Natl Acad Sci U S A
February 1, 2000

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.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 1, 2000

Volume

97

Issue

3

Start / End Page

1119 / 1124

Location

United States

Related Subject Headings

  • Transfection
  • Recombinant Fusion Proteins
  • Receptors, Vasoactive Intestinal Peptide
  • Receptors, Opioid, mu
  • Receptors, Muscarinic
  • Receptors, Endothelin
  • Receptors, Cell Surface
  • Receptors, Angiotensin
  • Receptors, Adrenergic, beta
  • Receptor, Endothelin B
 

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Claing, A., Perry, S. J., Achiriloaie, M., Walker, J. K., Albanesi, J. P., Lefkowitz, R. J., & Premont, R. T. (2000). Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc Natl Acad Sci U S A, 97(3), 1119–1124. https://doi.org/10.1073/pnas.97.3.1119
Claing, A., S. J. Perry, M. Achiriloaie, J. K. Walker, J. P. Albanesi, R. J. Lefkowitz, and R. T. Premont. “Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity.Proc Natl Acad Sci U S A 97, no. 3 (February 1, 2000): 1119–24. https://doi.org/10.1073/pnas.97.3.1119.
Claing A, Perry SJ, Achiriloaie M, Walker JK, Albanesi JP, Lefkowitz RJ, et al. Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1119–24.
Claing, A., et al. “Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity.Proc Natl Acad Sci U S A, vol. 97, no. 3, Feb. 2000, pp. 1119–24. Pubmed, doi:10.1073/pnas.97.3.1119.
Claing A, Perry SJ, Achiriloaie M, Walker JK, Albanesi JP, Lefkowitz RJ, Premont RT. Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1119–1124.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 1, 2000

Volume

97

Issue

3

Start / End Page

1119 / 1124

Location

United States

Related Subject Headings

  • Transfection
  • Recombinant Fusion Proteins
  • Receptors, Vasoactive Intestinal Peptide
  • Receptors, Opioid, mu
  • Receptors, Muscarinic
  • Receptors, Endothelin
  • Receptors, Cell Surface
  • Receptors, Angiotensin
  • Receptors, Adrenergic, beta
  • Receptor, Endothelin B