Casein kinase I associates with members of the centaurin-alpha family of phosphatidylinositol 3,4,5-trisphosphate-binding proteins.
Mammalian casein kinases I (CKI) belong to a family of serine/threonine protein kinases involved in diverse cellular processes including cell cycle progression, membrane trafficking, circadian rhythms, and Wnt signaling. Here we show that CKIalpha co-purifies with centaurin-alpha(1) in brain and that they interact in vitro and form a complex in cells. In addition, we show that the association is direct and occurs through the kinase domain of CKI within a loop comprising residues 217-233. These residues are well conserved in all members of the CKI family, and we show that centaurin-alpha(1) associates in vitro with all mammalian CKI isoforms. To date, CKIalpha represents the first protein partner identified for centaurin-alpha(1). However, our data suggest that centaurin-alpha(1) is not a substrate for CKIalpha and has no effect on CKIalpha activity. Centaurin-alpha(1) has been identified as a phosphatidylinositol 3,4,5-trisphosphate-binding protein. Centaurin-alpha(1) contains a cysteine-rich domain that is shared by members of a newly identified family of ADP-ribosylation factor guanosine trisphosphatase-activating proteins. These proteins are involved in membrane trafficking and actin cytoskeleton rearrangement, thus supporting a role for CKIalpha in these biological events.
University of Edinburgh, Division of Biomedical and Clinical Laboratory Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD.
T
T
Dubois
P
P
Kerai
E
E
Zemlickova
S
S
Howell
T R
TR
Jackson
K
K
Venkateswarlu
P J
PJ
Cullen
A B
AB
Theibert
L
L
Larose
P J
PJ
Roach
A
A
Aitken
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D047388:Casein Kinases; D002453:Cell Cycle; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D020690:GTPase-Activating Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D013058:Mass Spectrometry; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D000199:Actins; C491062:Adap1 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D018129:Phosphatidylinositol Phosphates; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; D005982:Glutathione Transferase; D011494:Protein Kinases; D047388:Casein Kinases; D003545:Cysteine