Induction of apoptosis by SLK, a Ste20-related kinase.
We have cloned and characterized a novel murine Ste20-related kinase designated SLK. SLK displays high homology to the Ste20-related kinase LOK, and is more distantly related to MST1 and 2, both Ste20-like kinases. In addition, SLK displays high homology to microtubule and nuclear associated protein (M-NAP) and AT1-46, both of unknown function. SLK is ubiquitously expressed as multiple mRNAs in tissues and cell lines and is downregulated by mitogen depletion in differentiating myoblasts. Biochemical characterization showed that SLK overexpression activates c-Jun amino-terminal kinase 1 (JNK1). However, in vitro kinase assays indicated that SLK was not activated in response to various growth factors or stress-inducing agents. Immunofluorescence studies revealed that SLK colocalized to distinct cytosolic domains, preferentially at the periphery of the cells. In addition, prolonged overexpression of SLK in cultured fibroblasts resulted in apoptosis as demonstrated by annexin-V and TUNEL staining. Our results suggest that SLK belongs to a new family of protein kinases, mediating activation of the stress response pathway through a novel signaling cascade.
Sabourin
L A
LA
MOBIX, Institute for Molecular Biology and Biotechnology, McMaster University, Hamilton, Ontario, Canada.
Rudnicki
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MA
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D016259:Genes, myc; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013347:Subcellular Fractions; D000099317:Hippo Kinases
D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C402650:SLK protein, mouse; D000099317:Hippo Kinases; C078754:STE20 protein, S cerevisiae