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J. Cell Biol. 164 (4): 527-534

Copyright © 2004 by the Rockefeller University Press.

Article

Bicarbonate-responsive "soluble" adenylyl cyclase defines a nuclear cAMP microdomain

Jonathan H. Zippin1,2, Jeanne Farrell1, David Huron1, Margarita Kamenetsky1, Kenneth C. Hess1, Donald A. Fischman3, Lonny R. Levin1, , and Jochen Buck1

1 Department of Pharmacology, Joan and Sanford I. Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021
2 Tri-Institutional MD/PhD Program, Joan and Sanford I. Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021
3 Department of Cell and Developmental Biology, Joan and Sanford I. Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021

Address correspondence to Lonny R. Levin, Dept. of Pharmacology, Joan and Sanford I. Weill Medical College and Graduate School of Medical Sciences of Cornell University, 1300 York Ave., New York, NY 10021. Tel.: (212) 746-6752. Fax: (212) 747-6241. email: llevin{at}med.cornell.edu

Abstract: Bicarbonate-responsive "soluble" adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation.

Key Words: CREB; PKA; gene expression; compartmentalization; signal transduction

Abbreviations used in this paper: CREB, cAMP response element binding protein; PKA, protein kinase A; sAC, soluble adenylyl cyclase; tmAC, transmembrane adenylyl cyclase.

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