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J. Biol. Chem. 283 (18): 12665-12673

© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

CKI{alpha} Is Associated with and Phosphorylates Star-PAP and Is Also Required for Expression of Select Star-PAP Target Messenger RNAs*

Michael L. Gonzales, David L. Mellman, , and Richard A. Anderson1

Molecular and Cellular Pharmacology Training Program, Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706

Abstract: We have recently identified Star-PAP, a nuclear poly(A) polymerase that associates with phosphatidylinositol-4-phosphate 5-kinase I{alpha} (PIPKI{alpha}) and is required for the expression of a specific subset of mRNAs. Star-PAP activity is directly modulated by the PIPKI{alpha} product phosphatidylinositol 4,5-bisphosphate (PI-4,5-P2), linking nuclear phosphoinositide signaling to gene expression. Here, we show that PI-4,5-P2-dependent protein kinase activity is also a part of the Star-PAP protein complex. We identify the PI-4,5-P2-sensitive casein kinase I{alpha} (CKI{alpha}) as a protein kinase responsible for this activity and further show that CKI{alpha} is capable of directly phosphorylating Star-PAP. Both CKI{alpha} and PIPKI{alpha} are required for the synthesis of some but not all Star-PAP target mRNA, and like Star-PAP, CKI{alpha} is associated with these messages in vivo. Taken together, these data indicate that CKI{alpha}, PIPKI{alpha}, and Star-PAP function together to modulate the production of specific Star-PAP messages. The Star-PAP complex therefore represents a location where multiple signaling pathways converge to regulate the expression of specific mRNAs.

Received for publication January 25, 2008. Revision received February 20, 2008.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed: Dept. of Pharmacology, University of Wisconsin, 1300 University Ave., Rm. 3750 MSC, Madison, WI 53706. Tel.: 608-262-3753; Fax: 608-262-1257; E-mail: raanders{at}wisc.edu.

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