RESEARCH ARTICLE


GRK2-Deficiency Reduces Insulin Activation of ERK1/2 and Mitogenesis in Mouse Liver FL83B Cells



Gulnar Shahid, Tahir Hussain*
Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 521 Science and Research Bldg 2, Houston, TX 77204, USA.

Article Information


Identifiers and Pagination:

Year: 2009
Volume: 2
First Page: 44
Last Page: 47
Publisher Id: TODIAJ-2-44
DOI: 10.2174/1876524600902010044

Article History:

Received Date: 14/05/2009
Revision Received Date: 02/06/2009
Acceptance Date: 10/06/2009
Electronic publication date: 2/7/2009
Collection year: 2009

Shahid et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 521 Science and Research Bldg 2, Houston, TX 77204, USA. E-mail: augstein@diabetes-karlsburg.de


Abstract

We have reported that G protein coupled receptor kinase-2 (GRK2) negatively regulates insulin receptor signaling leading to glycogen synthesis in mouse liver derived FL83B cells. Since insulin is a potent cellular growth hormone, present study investigated the effect of GRK2 on insulin-stimulated MAP kinase pathway leading to mitogenesis. Specific GRK2 siRNA was used to knock-down (>90%) GRK2 in FL83B cells. Effect of insulin on ERK1/2 activation and [3H]-methyl thymidine incorporation were determined in GRK2 siRNA-treated and control cells. Insulinstimulated ERK1/2 activation was attenuated in GRK2-deficient as compared to control cells. Basal and insulinstimulated [3H]-methyl thymidine incorporation, a measure of mitogenesis, was lower in GRK2-deficient cells. The data suggest that GRK2 may have positive regulatory role in insulin-stimulated MAP kinase pathway and mitogenesis. The present study together with our earlier report on insulin-induced glycogen synthesis indicates a dual role of GRK2 in insulin receptor signaling/function.