3pK, a novel mitogen-activated protein (MAP) kinase-activated protein kinase, is targeted by three MAP kinase pathways. 1996

S Ludwig, and K Engel, and A Hoffmeyer, and G Sithanandam, and B Neufeld, and D Palm, and M Gaestel, and U R Rapp
Institut für Medizinische Strahlenkunde und Zellforschung, Würzburg, Germany. IMSD019@rzbox.uni-wuerzburg.de

Recently we have identified a mitogen-activated protein kinase (MAPK)-activated protein kinase, named 3pK (G. Sithanandam, F. Latif, U. Smola, R. A. Bernal, F.-M. Duh, H. Li, I. Kuzmin, V. Wixler, L. Geil, S. Shresta, P. A. Lloyd, S. Bader, Y. Sekido, K. D. Tartof, V. I. Kashuba, E. R. Zabarovsky, M. Dean, G. Klein, B. Zbar, M. I. Lerman, J. D. Minna, U. R. Rapp, and A. Allikmets, Mol. Cell. Biol. 16:868-876, 1996). In vitro characterization of the kinase revealed that 3pK is activated by ERK. It was further shown that 3pK is phosphorylated in vivo after stimulation of cells with serum. However, the in vivo relevance of this observation in terms of involvement of the Raf/MEK/ERK cascade has not been established. Here we show that 3pK is activated in vivo by the growth inducers serum and tetradecanoyl phorbol acetate in promyelocytic HL60 cells and transiently transfected embryonic kidney 293 cells. Activation of 3pK was Raf dependent and was mediated by the Raf/MEK/ERK kinase cascade. 3pK was also shown to be activated after stress stimulation of cells. In vitro studies with recombinant proteins demonstrate that in addition to ERK, members of other subgroups of the MAPK family, namely, p38RK and Jun-N-terminal kinases/stress-activated protein kinases, were also able to phosphorylate and activate 3pK. Cotransfection experiments as well as the use of a specific inhibitor of p38RK showed that these in vitro upstream activators also function in vivo, identifying 3pK as the first kinase to be activated through all three MAPK cascades. Thus, 3pK is a novel convergence point of different MAPK pathways and could function as an integrative element of signaling in both mitogen and stress responses.

UI MeSH Term Description Entries
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D017346 Protein Serine-Threonine Kinases A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D047908 Intracellular Signaling Peptides and Proteins Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors. Intracellular Signaling Peptides,Intracellular Signaling Proteins,Peptides, Intracellular Signaling,Proteins, Intracellular Signaling,Signaling Peptides, Intracellular,Signaling Proteins, Intracellular
D017871 Calcium-Calmodulin-Dependent Protein Kinases A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277) Ca(2+)-Calmodulin-Dependent Protein Kinase,Calcium-Calmodulin-Dependent Protein Kinase,Calmodulin-Dependent Protein Kinase,Calmodulin-Dependent Protein Kinases,Multifunctional Calcium-Calmodulin-Dependent Protein Kinase,Restricted Calcium-Calmodulin-Dependent Protein Kinase,Calcium-Calmodulin-Dependent Protein Kinases, Multifunctional,Calcium-Calmodulin-Dependent Protein Kinases, Restricted,Calmodulin-Dependent Multiprotein Kinase,Calmodulin-Kinase,Cam-MPK,Multifunctional Calcium-Calmodulin-Dependent Protein Kinases,Restricted Calcium-Calmodulin-Dependent Protein Kinases,Calcium Calmodulin Dependent Protein Kinase,Calcium Calmodulin Dependent Protein Kinases, Multifunctional,Calcium Calmodulin Dependent Protein Kinases, Restricted,Calmodulin Dependent Multiprotein Kinase,Calmodulin Dependent Protein Kinase,Calmodulin Dependent Protein Kinases,Calmodulin Kinase,Cam MPK,Kinase, Calcium-Calmodulin-Dependent Protein,Kinase, Calmodulin-Dependent Protein,Multifunctional Calcium Calmodulin Dependent Protein Kinase,Multifunctional Calcium Calmodulin Dependent Protein Kinases,Multiprotein Kinase, Calmodulin-Dependent,Protein Kinase, Calcium-Calmodulin-Dependent,Protein Kinase, Calmodulin-Dependent,Protein Kinases, Calcium-Calmodulin-Dependent,Protein Kinases, Calmodulin-Dependent,Restricted Calcium Calmodulin Dependent Protein Kinase,Restricted Calcium Calmodulin Dependent Protein Kinases
D018882 Heat Stress Disorders A group of conditions that develop due to overexposure or overexertion in excessive environmental heat. Exertional Heat Illness,Exertional Heat Stress,Heat Cramps,Heat Fatigue,Heat Illness,Heat Stress Syndromes,Heat Syncope,Stress Disorders, Heat,Exertional Heat Illnesses,Exertional Heat Stresses,Fatigue, Heat,Heat Cramp,Heat Fatigues,Heat Illness, Exertional,Heat Illnesses,Heat Stress Disorder,Heat Stress Syndrome,Heat Stress, Exertional,Heat Syncopes,Illness, Heat,Stress Disorder, Heat,Stress Syndrome, Heat,Syncope, Heat
D018922 HL-60 Cells A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8) HL60 Cells,Cell, HL60,Cells, HL60,HL 60 Cells,HL-60 Cell,HL60 Cell

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