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PCTAIRE-1

Characterization, Subcellular Distribution, and Cell Cycle-dependent Kinase Activity

Department of Oncology, Novartis Pharma AG, 4002 Basel, Switzerland [S. C., I. C., K. W-C., S. F.], and Friedrich Miescher Institute, 4057 Basel, Switzerland [J. H.]

PCTAIRE-1 is a member of the cyclin-dependent kinase (cdk) family whose function is unknown. We examined the pattern of PCTAIRE-1 protein expression in a number of normal and transformed cell lines of various origins and found that the kinase is ubiquitous. Indirect immunofluorescence indicated that PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle. Confocal microscopy showed that PCTAIRE-1 does not colocalize with components of the cytoskeleton or with the endoplasmic reticulum. We found that endogenous PCTAIRE-1 and ectopically expressed PCTAIRE-1 display kinase activity when myelin basic protein is used as an acceptor substrate. Similar to other members of the cyclin-dependent kinase family, PCTAIRE-1 seems to require binding to a regulatory subunit to display kinase activity. PCTAIRE-1 activity is cell cycle dependent and displays a peak in the S and G₂ phases. We show that the low level of kinase activity observed until the onset of S phase correlates with elevated tyrosine phosphorylation of the molecule.

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