Northern blot analysis detected highest expression of PBK in placenta, with lower expression in heart and pancreas and very low expression in skeletal muscle, kidney, liver, and lung no expression was detected in adult brain. The PBK protein has active-site sequences conserved in serine/threonine or dual-specificity kinases, as well as a C-terminal PDZ domain-binding ETDV motif. Using DLG (DLG1 601014) as bait in a yeast 2-hybrid screen, followed by PCR of a HeLa cell cDNA library, Gaudet et al. RT-PCR detected TOPK in activated, but not deactivated, T-LAK cells.
Northern blot analysis of 12 human tissues detected transcripts of 1.9 and 2 kb in testis only. The variants differ at their 5-prime ends and encode the same protein, a deduced 322-amino acid serine/threonine kinase with a calculated molecular mass of 37.4 kD. (2000) cloned 2 variants of PBK, which they called TOPK. Regulatory mechanisms of mitogen-activated kinase signaling.By screening for genes upregulated during activation of lymphokine-activated killer T (T-LAK) cells, Abe et al. Molecular recognitions in MAP kinase cascades. The MEK/ERK cascade: From signaling specificity to diverse functions. Regulation of the immune response by stress-activated protein kinases. J Cell Sci 118: 3569–3572 ĭifferential regulation and properties of MAPKs. Integrating signals from RTKs to ERK/MAPK. The MAP kinase signaling cascades: A system of hundreds of components regulates a diverse array of physiological functions. The c-Jun kinase/stress-activated pathway: Regulation, function and role in human disease. Regulation of JNK and p38 MAPK in the immune system: Signal integration, propagation and termination. Scaffold proteins: Hubs for controlling the flow of cellular information.
Dhanasekaran DN, Kashef K, Lee CM, Xu H, Reddy EP. Role of mitogen-activated protein kinase kinase kinases in signal integration. P38 MAP-kinases pathway regulation, function and role in human diseases. Mechanisms and functions of p38 MAPK signalling. MAPKKs for the classic ERK1/2 module are MEK1 and MEK2, and the MAPKKKs include members of the Raf family, Mos, and Tpl2.Ī conserved motif at the amino termini of MEKs might mediate high-affinity interaction with the cognate MAPKs. Important upstream regulators of this module include cell surface receptors, such as receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and integrins, as well as the small GTPases Ras and Rap. 2) responds primarily to growth factors and mitogens to induce cell growth and differentiation ( McKay and Morrison 2007 Shaul and Seger 2007). ERK family members possess a TEY motif in the activation segment and can be subdivided into two groups: the classic ERKs that consist mainly of a kinase domain (ERK1 and ERK2) and the larger ERKs (such as ERK5) that contain a much more extended sequence carboxy-terminal to their kinase domain ( Zhang and Dong 2007). In mammals, these are ERKs (extracellular-signal-regulated kinases), JNKs (Jun amino-terminal kinases), and p38/SAPKs (stress-activated protein kinases). The MAP kinases can be grouped into three main families. MAPKs generally contain docking sites for MAPKKs and substrates, which allow high-affinity protein–protein interactions to ensure both that they are activated by a particular upstream MAPKK ( Bardwell and Thorner 1996) and that they recognize specific downstream targets ( Tanoue and Nishida 2003). Once activated, the MAPK phosphorylates diverse substrates in the cytosol and nucleus to bring about changes in protein function and gene expression that execute the appropriate biological response. The MAPKKK directly phosphorylates and activates the MAPKK, which, in turn, activates the MAPK by dual phosphorylation of a conserved tripeptide TxY motif in the activation segment. The MAPKKK is typically activated by interactions with a small GTPase and/or phosphorylation by protein kinases downstream from cell surface receptors ( Cuevas et al. Each cascade is initiated by specific extracellular cues and leads to activation of a particular MAPK following the successive activation of a MAPK kinase kinase (MAPKKK) and a MAPK kinase (MAPKK) ( Fig. 3DLABPRINT P38 NORMAL OR HIGH SERIES
Mitogen-activated protein kinase (MAPK) modules containing three sequentially activated protein kinases are key components of a series of vital signal transduction pathways that regulate processes such as cell proliferation, cell differentiation, and cell death in eukaryotes from yeast to humans ( Fig.
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