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The cyclin-dependent kinases (Cdks) are 34 kDa catalytic subunits that require regulatory cyclin subunits to manifest their serine/threonine kinase activity. As a group, the Cdks (prototype Cdc2 [Cdkl]) are believed to regulate key cell cycle transitions. A human Cdk4 cDNA, initially cloned based on homology to nucleotide sequences conserved within known serine/threonine kinases and termed PSK-J3, is now recognized to be a major but nonexclusive catalytic partner for mammalian D-type G1 cyclins. The Cdk4 kinase can be activated by cyclins Dl, D2 and D3, but not by cyclins A, B1, or E. Like other Cdks, Cdk4 consists essentially of a catalytic domain only. Cyclins are presumed to act as regulatory subunits in vivo. Cdk4 expression in tissues has not been well documented. The enzyme is expressed in a variety of cultured cell lines, including fibroblasts, T cells, macrophages, and other cells of the myeloid lineage, and may be ubiquitous. Its levels of synthesis oscillate minimally during the cell cycle, being highest during late G1 and early S phase, and the protein is quite stable. In proliferating cells, Cdk4 forms persistent complexes with regulatory D-type cyclin subunits. In contrast to the catalytic subunit, D-type cyclins in these complexes turn over rapidly.