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

Audrey Claing, Stephen J. Perry, Mircea Achiriloaie, Julia K L Walker, Joseph P. Albanesi, Robert J. Lefkowitz, Richard T. Premont

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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 β2-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 β-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.

Original languageEnglish (US)
Pages (from-to)1119-1124
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number3
DOIs
StatePublished - Feb 1 2000

Fingerprint

G-Protein-Coupled Receptors
Clathrin
GTP-Binding Proteins
G-Protein-Coupled Receptor Kinases
ADP-Ribosylation Factors
Dynamins
Arrestin
GTPase-Activating Proteins
Proteins
Transferrin
Epidermal Growth Factor Receptor
Adrenergic Receptors

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. / Claing, Audrey; Perry, Stephen J.; Achiriloaie, Mircea; Walker, Julia K L; Albanesi, Joseph P.; Lefkowitz, Robert J.; Premont, Richard T.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 3, 01.02.2000, p. 1119-1124.

Research output: Contribution to journalArticle

Claing, Audrey ; Perry, Stephen J. ; Achiriloaie, Mircea ; Walker, Julia K L ; Albanesi, Joseph P. ; Lefkowitz, Robert J. ; Premont, Richard T. / Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 3. pp. 1119-1124.
@article{6fb3b13d599c4be49083de8e2e5f59d3,
title = "Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity",
abstract = "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 β2-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 β-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.",
author = "Audrey Claing and Perry, {Stephen J.} and Mircea Achiriloaie and Walker, {Julia K L} and Albanesi, {Joseph P.} and Lefkowitz, {Robert J.} and Premont, {Richard T.}",
year = "2000",
month = "2",
day = "1",
doi = "10.1073/pnas.97.3.1119",
language = "English (US)",
volume = "97",
pages = "1119--1124",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "3",

}

TY - JOUR

T1 - Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity

AU - Claing, Audrey

AU - Perry, Stephen J.

AU - Achiriloaie, Mircea

AU - Walker, Julia K L

AU - Albanesi, Joseph P.

AU - Lefkowitz, Robert J.

AU - Premont, Richard T.

PY - 2000/2/1

Y1 - 2000/2/1

N2 - 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 β2-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 β-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.

AB - 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 β2-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 β-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.

UR - http://www.scopus.com/inward/record.url?scp=0033973475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033973475&partnerID=8YFLogxK

U2 - 10.1073/pnas.97.3.1119

DO - 10.1073/pnas.97.3.1119

M3 - Article

VL - 97

SP - 1119

EP - 1124

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 3

ER -