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

Claing, A

Perry, SJ

Achiriloaie, M

Walker, JK

Albanesi, JP

Lefkowitz, RJ

Premont, RT

United States

2013-09-05T17:48:57Z

2000-02-01

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.

https://www.ncbi.nlm.nih.gov/pubmed/10655494

0027-8424

https://hdl.handle.net/10161/7812

eng

Proceedings of the National Academy of Sciences

Proc Natl Acad Sci U S A

Adaptor Proteins, Signal Transducing

Animals

COS Cells

Cell Cycle Proteins

Cells, Cultured

Cercopithecus aethiops

Cyclic AMP

Endocytosis

GTP-Binding Proteins

GTPase-Activating Proteins

Humans

Phosphoproteins

Receptor, Angiotensin, Type 1

Receptor, Angiotensin, Type 2

Receptor, Endothelin B

Receptors, Adrenergic, beta

Receptors, Angiotensin

Receptors, Cell Surface

Receptors, Endothelin

Receptors, Muscarinic

Receptors, Opioid, mu

Receptors, Vasoactive Intestinal Peptide

Recombinant Fusion Proteins

Transfection

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

Journal article

Lefkowitz, RJ|0000-0003-1472-7545

Premont, RT|0000-0002-8053-5026

https://www.ncbi.nlm.nih.gov/pubmed/10655494

1119

1124

3

Basic Science Departments

Biochemistry

Chemistry

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Medicine, Gastroenterology

Pathology

School of Medicine

School of Nursing

Trinity College of Arts & Sciences

University Institutes and Centers

Published

97