Casein Kinase I Associates with Members of the Centaurin-α Family of Phosphatidylinositol 3,4,5-Trisphosphate-binding Proteins

Abstract

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 CKI␣ co-purifies with centaurin-␣ 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-␣ 1 associates in vitro with all mammalian CKI isoforms. To date, CKI␣ represents the first protein partner identified for centaurin-␣ 1 . However, our data suggest that centaurin-␣ 1 is not a substrate for CKI␣ and has no effect on CKI␣ activity. Centaurin-␣ 1 has been identified as a phosphatidylinositol 3,4,5-trisphosphate-binding protein. Centaurin-␣ 1 contains a cysteine-rich domain that is shared by members of a newly identified family of ADPribosylation factor guanosine trisphosphatase-activating proteins. These proteins are involved in membrane trafficking and actin cytoskeleton rearrangement, thus supporting a role for CKI␣ in these biological events.

Centaurin-α1 interacts directly with kinesin motor protein KIF13B

“…Centaurin-α 1 interacts with both CK1α and PKC but is only phosphorylated by PKC (Dubois et al, 2001;Zemlickova et al, 2003) whereas KIF13B is phosphorylated by several unidentified kinases (Hanada et al, 2000). In this respect, it is worth noting here that PtdIns(3,4,5)P 3 , ARF6 and PKC isoforms have been shown to concentrate at the leading edges of the cell surface in order to regulate cell adhesion and migration (Sabe, 2003;Ridley et al, 2003).…”

“…Therefore, identification of the binding partners of centaurin-α 1 and their localization within the cell might provide clues to the cellular functions of centaurin-α 1 in vivo. For example, the casein kinase 1α (CK1α) and protein kinase C (PKC) isoforms have recently been shown to interact with centaurin-α 1 ; however, the functional consequences of these interactions have not been fully characterized (Dubois et al, 2001;Zemlickova et al, 2003). In this manuscript, we present evidence that centaurin-α 1 binds to a kinesin motor protein termed KIF13B.…”

PI-3-kinase-dependent membrane recruitment of centaurin-α2 is essential for its effect on ARF6-mediated actin cytoskeleton reorganisation

“…Centaurin-␣ 1 expression is increased in neurons of patients with Alzheimer's disease (AD) (Reiser and Bernstein, 2002). Moreover, it interacts with casein kinase I␣, which hyperphosphorylates the ␤-amyloid precursor protein in the brains of AD patients (Dubois et al, 2001). To date, the significance of the increase in centaurin-␣ 1 protein expression in terms of AD pathology is unknown.…”

RanBPM, a novel interaction partner of the brain‐specific protein p42IP4/centaurin α‐1

“…p42 IP4 can shuttle between cytosol, nucleus and plasma membrane, depending on the cell stimulation situation . Several interaction partners of p42 IP4 have been identified, such as casein kinase I (Dubois et al 2001(Dubois et al , 2002, nucleolin , protein kinase C , several ARFs (Thacker et al 2004;Venkateswarlu et al 2004) GAKIN (Venkateswarlu et al 2005;Horiguchi et al 2006), the peptidase nardilysin (Stricker et al 2006) or F-actin (Thacker et al 2004). It has been shown that p42 IP4 is a component of the neuronal phosphatidyl inositol 3-kinase cascade and is involved in dendritic differentiation/synaptic plasticity and/or transport of PtdIns(3,4,5)P 3 -containing vesicles along axons to regulate neuronal cell polarity (Horiguchi et al 2006;Moore et al 2007).…”