Cloning and Characterization of a Human STE20-like Protein Kinase with Unusual Cofactor Requirements
| Autor: | Karin Schinkmann, John Blenis |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Molecular Sequence Data Coenzymes Protein Serine-Threonine Kinases Mitogen-activated protein kinase kinase Biochemistry MAP2K7 Mice Adenosine Triphosphate GTP-Binding Proteins Animals Humans Magnesium ASK1 Amino Acid Sequence c-Raf Cloning Molecular Molecular Biology Manganese Base Sequence biology MAP kinase kinase kinase Cyclin-dependent kinase 4 fungi Cyclin-dependent kinase 2 Intracellular Signaling Peptides and Proteins 3T3 Cells Cell Biology MAP Kinase Kinase Kinases biology.protein Cyclin-dependent kinase 9 Guanosine Triphosphate human activities HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 272:28695-28703 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.272.45.28695 |
| Popis: | We cloned and characterized a novel human member of the STE20 serine/threonine protein kinase family named mst-3. Based on its domain structure, mst-3 belongs to the SPS1 subgroup of STE20-like proteins, which includes germinal center (GC) kinase, hematopoietic progenitor kinase (HPK), kinase homologous to STE20/SPS-1 (KHS), kinases responsive to stress (KRS1/2), the mammalian STE20-like kinases (mst1/2), and the recently published STE20/oxidant stress response kinase SOK-1. mst-3 is most closely related to SOK-1, with 88% amino acid similarity in the kinase domain. The similarity of the mst-3 kinase domain to STE20 is 42%. The mst-3 transcript is ubiquitously expressed, and the protein was found in all human, mouse, and monkey cell lines tested. An in vitro kinase assay showed that mst-3 can phosphorylate basic exogenous substrates as well as itself. Interestingly, mst-3 prefers Mn2+ to Mg2+ as a divalent cation and can use both GTP and ATP as phosphate donors. Like SOK-1, mst-3 is activated by autophosphorylation. However, a physiological stimulus of mst-3 activity was not identified. mst-3 activity does not change upon exposure to several mitogenic and stress stimuli. Overexpression of mst-3 wild-type or kinase dead protein affects neither the extracellular signal-regulated kinases (ERK1/2 or ERK6), c-Jun N-terminal kinase (JNK), p38, nor pp70S6 kinase, suggesting that mst-3 is part of a novel signaling pathway. |
| Databáze: | OpenAIRE |
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