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

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    154.8 Kb
    Date
    2000-02-01
    Authors
    Achiriloaie, M
    Albanesi, JP
    Claing, A
    Lefkowitz, Robert J
    Perry, SJ
    Premont, Richard Thomas
    Walker, JK
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    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 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.
    Type
    Journal article
    Subject
    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
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    https://hdl.handle.net/10161/7812
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    Scholars@Duke

    Lefkowitz

    Robert J. Lefkowitz

    James B. Duke Distinguished Professor of Medicine
    The focus of work in this laboratory is on the elucidation of the molecular properties and regulatory mechanisms controlling the function of G protein-coupled receptors. As model systems we utilize the so called adrenergic receptors for adrenaline and related molecules. The goal is to learn the general principles of signal transduction from the outside to the inside of the cell which are involved in systems as diverse as sensory perception, neuro- transmitter and hormonal signaling. Stud
    Premont

    Richard Thomas Premont

    Associate Professor in Medicine
    Critical physiological events throughout the body are controlled by extracellular signals from neurotransmitters and hormones acting on cell surface receptors. Receptors transduce these signals to alter intracellular metabolism and cellular responsiveness through heterotrimeric G protein/second messenger pathways or through small GTP-binding protein/protein kinase cascades. The mechanisms that control the responsiveness of target organ G protein-coupled receptors include receptor ph
    Alphabetical list of authors with Scholars@Duke profiles.
    Open Access

    Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy

    Rights for Collection: Scholarly Articles

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