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Gene Review:

SLK - STE20-like kinase

Homo sapiens

Synonyms: CTCL tumor antigen se20-9, KIAA0204, LOSK, STE20-like serine/threonine-protein kinase, STE20-related kinase, ...

Hao, W. et al., Yamada, E. et al., Zhou, T.H. et al., Nör, J.E. et al., Cybulsky, A.V. et al., et al.

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Disease relevance of SLK

Chemical anoxia and recovery during re-exposure to glucose (ischemia-reperfusion injury in cell culture) stimulated SLK activity [1].
In this study, we implanted sponges seeded with OSCC-3 (oral squamous cell carcinoma) or SLK (Kaposi's sarcoma) together with endothelial cells into SCID mice to generate human tumors vascularized with human microvessels [2].

High impact information on SLK

Thus, SLK is an anoxia/recovery-dependent kinase that is activated via homodimerization and that signals via ASK1 and p38 to promote apoptosis [1].
In contrast, the C-terminal domain of SLK did not dimerize with a related kinase, Mst1, and did not affect Mst1 activity [1].
Overexpression of SLK enhanced anoxia/recovery-induced apoptosis, release of cytochrome c, and activities of caspase-8 and -9, and apoptosis was reduced significantly with p38 and caspase-9 inhibitors [1].
SLK underwent dimerization via the C-terminal domain, and dimerization enhanced SLK activity [1].
Phosphorylation/dephosphorylation of SLK were not associated with changes in kinase activity [1].

Biological context of SLK

The C-terminal domain of hSLK includes both the coiled-coil structure and four Pro/Glu/Ser/Thr-rich (PEST) sequences, but not the GTPase-binding domain (GBD) that is characteristic of the p21-activated kinase (PAK) family, polyproline consensus binding sites, or the Leu-rich domain seen in the group I germinal center kinases (GCKs) [3].
A novel isoform of mammalian STE20-like kinase 3 (MST3) with a different 5' coding region from MST3, termed MST3b, was identified by searching through expressed sequence tag data base and obtained by rapid amplification of cDNA 5'-ends [4].

Anatomical context of SLK

Northern blot analysis indicated that hSLK was ubiquitously expressed. hSLK overexpressed in COS-7 cells phosphorylates itself as well as myelin basic protein used as a substrate [3].
Attenuation of the protective aspects of the endoplasmic reticulum stress response by SLK may contribute to its proapoptotic effect [1].
Ste20-like kinase, SLK, a germinal center kinase found in kidney epithelial cells, signals to promote apoptosis [5].

Other interactions of SLK

Cloning and characterization of MST4, a novel Ste20-like kinase [6].

Analytical, diagnostic and therapeutic context of SLK

Molecular cloning and characterization of a novel human STE20-like kinase, hSLK [3].

References

Induction of apoptosis by the Ste20-like kinase SLK, a germinal center kinase that activates apoptosis signal-regulating kinase and p38. Hao, W., Takano, T., Guillemette, J., Papillon, J., Ren, G., Cybulsky, A.V. J. Biol. Chem. (2006) [Pubmed]
Up-Regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. Nör, J.E., Christensen, J., Liu, J., Peters, M., Mooney, D.J., Strieter, R.M., Polverini, P.J. Cancer Res. (2001) [Pubmed]
Molecular cloning and characterization of a novel human STE20-like kinase, hSLK. Yamada, E., Tsujikawa, K., Itoh, S., Kameda, Y., Kohama, Y., Yamamoto, H. Biochim. Biophys. Acta (2000) [Pubmed]
Identification of a human brain-specific isoform of mammalian STE20-like kinase 3 that is regulated by cAMP-dependent protein kinase. Zhou, T.H., Ling, K., Guo, J., Zhou, H., Wu, Y.L., Jing, Q., Ma, L., Pei, G. J. Biol. Chem. (2000) [Pubmed]
The 3'-untranslated region of the Ste20-like kinase SLK regulates SLK expression. Cybulsky, A.V., Takano, T., Papillon, J., Hao, W., Mancini, A., Di Battista, J.A., Cybulsky, M.I. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
Cloning and characterization of MST4, a novel Ste20-like kinase. Qian, Z., Lin, C., Espinosa, R., LeBeau, M., Rosner, M.R. J. Biol. Chem. (2001) [Pubmed]

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Slk	Rattus norvegicus

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