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.

Serum sialic acid, a reputed cardiovascular risk factor, is elevated in South Asian men compared to European men.

Serum total sialic acid (TSA) has recently been reported as a cardiovascular risk factor, but whether there are racial differences is not known. One hundred and twenty-four healthy young subjects (62 women and 62 men) were studied. Their age was 20.7 [0.9] years and they were matched for body mass index (BMI). Sixty-eight were of South Asian origin (37 women and 31 men) and 56 (25 women and 31 men) were European. Mean (SD) serum TSA was significantly higher in the South Asian men than the age-matched European men (74.3 [12.3] mg/dL versus 68.2 [13.0] mg/dL, P = 0.0198). In addition, serum TSA was significantly higher in South Asian women compared with European men (71.6 [8.9] mg/dL versus 68.2 [13.0] mg/dL, P = 0.0352). Finally, serum TSA was significantly higher in European women compared with European men (76.0 [13.1] mg/dL versus 69.2 [13.0] mg/dL, P = 0.008). We conclude that serum TSA may be worth measuring in different racial groups and also may be useful to assess individuals at risk of cardiovascular disease. Large prospective studies may help to explain why serum TSA is a reputed cardiovascular risk factor and shows racial differences.

Structure and sites of phosphorylation of 14-3-3 protein: role in coordinating signal transduction pathways.

The 14-3-3 family are homo- and heterodimeric proteins whose biological role has been unclear for some time, although they are now gaining acceptance as a novel type of 'adaptor' protein that modulates interactions between components of signal transduction pathways, rather than by direct activation or inhibition. It is becoming apparent that phosphorylation of the binding partner and possibly also the 14-3-3 proteins may regulate these interactions. 14-3-3 isoforms interact with a novel phosphoserine (Sp) motif on many proteins, RSX1,2SpXP. The two isoforms that interact with Raf-1 are phosphorylated in vivo on Ser185 in a consensus sequence motif for proline-directed kinases. The crystal structure of 14-3-3 indicates that this phosphorylation could regulate interaction of 14-3-3 with its target proteins. We have now identified a number of additional phosphorylation sites on distinct mammalian and yeast isoforms.