Activator Of S-Phase Kinase (ASK)

ASK interacts with CDC7L1 in mammalian cells and that these proteins form a complex in vivo. The authors showed that motif C of ASK is essential but not sufficient for the interaction of ASK with the CDC7L1 catalytic subunit. In an in vitro assay, ASK stimulated the kinase activity of CDC7L1, with the ASK and CDC7L1 complex capable of phosphorylating MCM2. Immunodepletion of ASK protein from cell extracts was accompanied by loss of nearly all CDC7L1-dependent kinase activity, suggesting that ASK is the major activator of CDC7L1. Expression of ASK was regulated by growth factor stimulation, with the mRNA level low during the quiescent state and increasing as the cell entered S phase. ASK protein was extensively phosphorylated during S phase, presumably by CDC7L1.