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Molecular and Cellular Biology, June 2006, p. 4586-4600, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.01422-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Subcellular Localization and Biological Actions of Activated RSK1 Are Determined by Its Interactions with Subunits of Cyclic AMP-Dependent Protein Kinase{dagger}

Deepti Chaturvedi,{ddagger} Helen M. Poppleton,{ddagger},§ Teresa Stringfield, Ann Barbier,|| and Tarun B. Patel*

Department of Pharmacology,1 Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, Illinois 601532

Received 26 July 2005/ Returned for modification 8 September 2005/ Accepted 28 March 2006

Cyclic AMP (cAMP)-dependent protein kinase (PKA) and ribosomal S6 kinase 1 (RSK1) share several cellular proteins as substrates. However, to date no other similarities between the two kinases or interactions between them have been reported. Here, we describe novel interactions between subunits of PKA and RSK1 that are dependent upon the activation state of RSK1 and determine its subcellular distribution and biological actions. Inactive RSK1 interacts with the type I regulatory subunit (RI) of PKA. Conversely, active RSK1 interacts with the catalytic subunit of PKA (PKAc). Binding of RSK1 to RI decreases the interactions between RI and PKAc, while the binding of active RSK1 to PKAc increases interactions between PKAc and RI and decreases the ability of cAMP to stimulate PKA. The RSK1/PKA subunit interactions ensure the colocalization of RSK1 with A-kinase PKA anchoring proteins (AKAPs). Disruption of the interactions between PKA and AKAPs decreases the nuclear accumulation of active RSK1 and, thus, increases its cytosolic content. This subcellular redistribution of active RSK1 is manifested by increased phosphorylation of its cytosolic substrates tuberous sclerosis complex 2 and BAD by epidermal growth factor along with decreased cellular apoptosis.

* Corresponding author. Mailing address: Department of Pharmacology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153. Phone: (708) 216-5773. Fax: (708) 216-6888. E-mail: tpatel7{at}lumc.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} D.C. and H.M.P. are joint first authors.

§ Present address: Department of Developmental Neurobiology, St. Jude Children's Hospital, Memphis, TN 38105.

Present address: Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street, Indianapolis, IN 46229.

|| Present address: EnVivo Pharmaceuticals, 480 Arsenal St., Watertown, MA 02472.

Molecular and Cellular Biology, June 2006, p. 4586-4600, Vol. 26, No. 12
0270-7306/06/$08.00+0     doi:10.1128/MCB.01422-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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