Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase.

Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Research Abstract Details 

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Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Abstract Text:

Rana C Morris,Gary Z Morris,Weiqing Zhang,Merica Gellerman,Stephen J Beebe,

The C gamma and C alpha isoforms of the cAMP-dependent protein kinase (PKA) share 83% identity including all critical catalytic and substrate-binding residues defined to date. Compared to C alpha, C gamma has a different substrate specificity and a selective pseudosubstrate specificity, exhibiting inhibition by regulatory subunits, but not by the protein kinase inhibitor. In these studies, C gamma-mediated gene transcription regulation was compared with that of C alpha in four cell lines using transient transfection/dual luciferase assays. As compared to C gamma, C alpha more efficiently activated a cAMP-response element (CRE)-regulated fragment of the human alpha-glycoprotein hormone promoter which was coupled to a firefly luciferase reporter gene (pGH alpha-fluc). This occurred in Cos7, Y1, and Kin8 adrenal cells by 23-, 6.5-, and 1.4-fold, respectively. In contrast, C gamma, but not C alpha, activated the Sp1RE-regulated herpes simplex virus thymidine kinase promoter which was coupled to a Renilla luciferase reporter (pTK-rluc). In Sp1-deficient Sf9 cells, pGH alpha-fluc expression was maintained for both isoforms, but cotransfection with an Sp1 expression plasmid was necessary and sufficient for activation of pTK-rluc expression by C gamma. In all cell lines, cotransfection with a PDK1 expression plasmid enhanced the transcriptional activation of both C alpha and C gamma (1.5- to 3-fold), while a catalytically inactive PDK1 mutant (PDK.KD) did not. These results suggest that both C alpha and C gamma can activate CRE-responsive genes; however, C alpha does so with better efficiency than C gamma. In contrast to C alpha, C gamma activates transcription of genes containing pTK-like Sp1RE sites. Activation of different C subunit isoforms can provide a means to diversify cAMP-mediated transcription, possibly affecting cell phenotype.

Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Publishing Authors By Initials

RC Morris,GZ Morris,W Zhang,M Gellerman,SJ Beebe,

For similar proteins: fetal proteins: alpha-fetoproteins research abstracts see: proteins: fetal proteins: alpha-fetoproteins research

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Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Archives of biochemistry and biophysics

VOLUME: 403

Page Numbers: 219-28

Journal Abbreviation: Arch. Biochem. Biophys.

ISSN: 0003-9861

DAY: 15

MONTH: Jul

YEAR: 2002

Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Information

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LANGUAGE: eng

NlmUniqueID: 372430

Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Keywords Mesh Terms:

KEYWORDS: alpha-Fetoproteins

MESH TERMS: genetics

Chemical & Substance for Abstract: Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase. Information

Substance Name: AMP-activated protein kinases

Registry Number: EC 2.7.11.31

Grant and Affiliation Information for Differential transcriptional regulation by the alpha- and gamma-catalytic subunit isoforms of cAMP-dependent protein kinase.

AFFILIATION: Center for Pediatric Research, Eastern Virginia Medical School, 855 West Brambleton Avenue, Norfolk, VA 23510, USA.

Country: United States

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MEDLINETA: Arch Biochem Biophys

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