The Pleckstrin homology domain of CK2 interacting protein-1 is required for interactions and recruitment of protein kinase CK2 to the plasma membrane.
CKIP-1 is a recently identified interaction partner of protein kinase CK2 with a number of protein-protein interaction motifs, including an N-terminal pleckstrin homology domain. To test the hypothesis that CKIP-1 has a role in targeting CK2 to specific locations, we examined the effects of CKIP-1 on the localization of CK2. These studies demonstrated that CKIP-1 can recruit CK2 to the plasma membrane. Furthermore, the pleckstrin homology domain of CKIP-1 was found to be required for interactions with CK2 and for the recruitment of CK2 to the plasma membrane. In this regard, point mutations in this domain abolish membrane localization and compromise interactions with CK2. In addition, replacement of the pleckstrin homology domain with a myristoylation signal was insufficient to elicit any interaction with CK2. An investigation of the lipid binding of CKIP-1 reveals that it has broad specificity. A comparison with other pleckstrin homology domains revealed that the pleckstrin homology domain of CKIP-1 is distinct from other defined classes of pleckstrin homology domains. Finally, examination of CK2alpha for a region that mediates interactions with CKIP-1 revealed a putative HIKE domain, a complex motif found exclusively in proteins that bind pleckstrin homology domains. However, mutations within this motif were not able to abolish CKIP-1-CK2 interactions suggesting that this motif by itself may not be sufficient to mediate interactions. Overall, these results provide novel insights into how CK2, a predominantly nuclear enzyme, is targeted to the plasma membrane, and perhaps more importantly how it may be regulated.
Olsten
Mary Ellen K
ME
Departments of Biochemistry and Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
Canton
David A
DA
Zhang
Cunjie
C
Walton
Paul A
PA
Litchfield
David W
DW
D020816:Amino Acid Motifs; D001798:Blood Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D047390:Casein Kinase II; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D040681:Structural Homology, Protein
D001798:Blood Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human; D010750:Phosphoproteins; C039077:platelet protein P47; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases