The mitogen-activated protein kinases (MAPKs) and the cyclin-dependent kinases (CDKs) are key mediators of cell proliferation in response to extracellular signals. Recent additions to each of these families and the identification of kinases with structural features of both have provided insights into fundamental processes, such as cell division and differentiation. To identify novel serine kinases with features of MAPKs or CDKs, a degenerate PCR-based amplification approach was undertaken. The 57- and 52-kDa isoforms of a novel protein kinase, termed NKIATRE, were molecularly cloned from rat brain and jejunum cDNA libraries. Like the MAPKs, NKIATRE has a Thr-Xaa-Tyr motif in kinase subdomain VIII. NKIATRE also shows close homology to the cyclin-dependent kinase class of protein kinases and the cdc2-related kinases NKIAMRE, KKIALRE, and KKIAMRE, containing both conserved inhibitory phosphorylation sites and a putative cyclin-binding domain. Two isoforms of NKIATRE that differ in their carboxy-terminal ends have been identified. A functional nuclear localization signal is specific to the longer 57-kDa alpha isoform. Sequence similarity to the putative human tumor suppressor gene NKIAMRE, which is lost in leukemic patients with chromosome 5q deletions, suggests that NKIATRE may have a role in restricting cell growth or maintaining differentiation.
Copyright 2001 Academic Press.