Induction of apoptosis by SLK, a Ste20-related kinase

We have cloned and characterized a novel murine Ste20-related kinase design ated SLK, SLK displays high homology to the Ste20-related kinase LOK, and i s more distantly related to MST1 and 2, both Ste20-like kinases, In additio n, SLK displays high homology to microtubule and nuclear associated protein (M-NAP) and AT1-46, both of unknown function. SLK is ubiquitously expresse d as multiple mRNAs in tissues and cell lines and is downregulated by mitog en depletion in differentiating myoblasts, Biochemical characterization sho wed that SLK overexpression activates c-Jun amino-terminal kinase 1 (JNK1), However, in vitro kinase assays indicated that SLK was not activated in re sponse to various growth factors or stress-inducing agents. Immunofluoresce nce studies revealed that SLK colocalized to distinct cytosolic domains, pr eferentially at the periphery of the cells. In addition, prolonged overexpr ession 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.