RACK1 regulates specific functions of Gbetagamma

Songhai Chen; Edward J Dell; Fang Lin; Jiqing Sai; Heidi E Hamm

doi:10.1074/jbc.M313727200

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RACK1 regulates specific functions of Gbetagamma

Journal article

Open access

Peer reviewed

RACK1 regulates specific functions of Gbetagamma

Songhai Chen, Edward J Dell, Fang Lin, Jiqing Sai and Heidi E Hamm

The Journal of biological chemistry, Vol.279(17), pp.17861-17868

04/23/2004

DOI: 10.1074/jbc.M313727200

PMID: 14963031

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Abstract

We showed previously that Gbetagamma interacts with Receptor for Activated C Kinase 1 (RACK1), a protein that not only binds activated protein kinase C (PKC) but also serves as an adaptor/scaffold for many signaling pathways. Here we report that RACK1 does not interact with Galpha subunits or heterotrimeric G proteins but binds free Gbetagamma subunits released from activated heterotrimeric G proteins following the activation of their cognate receptors in vivo. The association with Gbetagamma promotes the translocation of RACK1 from the cytosol to the membrane. Moreover, binding of RACK1 to Gbetagamma results in inhibition of Gbetagamma-mediated activation of phospholipase C beta2 and adenylyl cyclase II. However, RACK1 has no effect on other functions of Gbetagamma, such as activation of the mitogen-activated protein kinase signaling pathway or chemotaxis of HEK293 cells via the chemokine receptor CXCR2. Similarly, RACK1 does not affect signal transduction through the Galpha subunits of G(i), G(s), or G(q). Collectively, these findings suggest a role of RACK1 in regulating specific functions of Gbetagamma.

Transfection

Signal Transduction

Lipid Metabolism

Humans

Neoplasm Proteins - physiology

Type C Phospholipases - metabolism

Receptors, Cell Surface

Neoplasm Proteins - metabolism

MAP Kinase Signaling System

Dose-Response Relationship, Drug

Phospholipase C beta

Isoenzymes - metabolism

Receptors for Activated C Kinase

Interleukin-8 - pharmacology

Cell Membrane - metabolism

GTP-Binding Protein beta Subunits - metabolism

Cyclic AMP - metabolism

Dimerization

Cell Line

GTP-Binding Protein gamma Subunits - metabolism

Gene Expression Regulation

Glutathione Transferase - metabolism

Adenylyl Cyclases - metabolism

Chemotaxis

Protein Transport

Hydrolysis

Microscopy, Confocal

Animals

Protein Binding

Cytosol - metabolism

Enzyme Activation

GTP-Binding Proteins

COS Cells

Microscopy, Fluorescence

Details

Title: Subtitle: RACK1 regulates specific functions of Gbetagamma
Creators: Songhai Chen - Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6600, USA. Songhai.Chen@Vanderbilt.edu
Edward J Dell
Fang Lin
Jiqing Sai
Heidi E Hamm
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.279(17), pp.17861-17868
DOI: 10.1074/jbc.M313727200
PMID: 14963031
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: CA34590-20 / NCI NIH HHS
Language: English
Date published: 04/23/2004
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040540002771

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