CKIalpha is associated with and phosphorylates star-PAP and is also required for expression of select star-PAP target messenger RNAs.
We have recently identified Star-PAP, a nuclear poly(A) polymerase that associates with phosphatidylinositol-4-phosphate 5-kinase Ialpha (PIPKIalpha) and is required for the expression of a specific subset of mRNAs. Star-PAP activity is directly modulated by the PIPKIalpha product phosphatidylinositol 4,5-bisphosphate (PI-4,5-P(2)), linking nuclear phosphoinositide signaling to gene expression. Here, we show that PI-4,5-P(2)-dependent protein kinase activity is also a part of the Star-PAP protein complex. We identify the PI-4,5-P(2)-sensitive casein kinase Ialpha (CKIalpha) as a protein kinase responsible for this activity and further show that CKIalpha is capable of directly phosphorylating Star-PAP. Both CKIalpha and PIPKIalpha are required for the synthesis of some but not all Star-PAP target mRNA, and like Star-PAP, CKIalpha is associated with these messages in vivo. Taken together, these data indicate that CKIalpha, PIPKIalpha, 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.
Gonzales
Michael L
ML
Molecular and Cellular Pharmacology Training Program, Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Mellman
David L
DL
Anderson
Richard A
RA
D000595:Amino Acid Sequence; D000818:Animals; D048128:Casein Kinase Ialpha / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011062:Polynucleotide Adenylyltransferase / Q000737:chemistry / Q000378:metabolism*; D011392:Proline; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017384:Sequence Deletion
D019269:Phosphatidylinositol 4,5-Diphosphate; D012333:RNA, Messenger; D011392:Proline; D011494:Protein Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D048128:Casein Kinase Ialpha; D009713:Nucleotidyltransferases; C586325:TUT1 protein, human; D011062:Polynucleotide Adenylyltransferase