Alternative titles; symbols
HGNC Approved Gene Symbol: STK25
Cytogenetic location: 2q37.3 Genomic coordinates (GRCh38): 2:241,492,670-241,509,572 (from NCBI)
Mitogen-activated protein kinase (MAPK; see 176948) cascades have been conserved throughout evolution. In mammals, these cascades allow responses to complex stimuli such as growth factors and inflammatory cytokines. In yeast, the Sterile 20 (Ste20) product functions upstream of the MAPK cascade. Using degenerate oligonucleotide primers based on known protein kinases, Pombo et al. (1996) cloned and characterized a human Ste20-like kinase, which they called Ste20/oxidant stress-response kinase-1 (SOK1) from human placenta. The SOK1 protein is 426 amino acids long and has a predicted molecular weight of approximately 48 kD. The SOK1 protein localized to the cytoplasm in NIH 3T3 fibroblasts. Using Northern blot analysis of rat organ mRNA, Pombo et al. (1996) showed that the SOK1 message was expressed in all tissues examined.
By RT-PCR using degenerate oligonucleotides based on conserved sequences in the kinase domains of yeast mitogen-activated protein kinase kinase kinases (MAPKKKs), Osada et al. (1997) isolated mouse brain cDNA fragments encoding kinase subdomains with significant sequence similarity to the kinase subdomains of yeast MAPKKKs. They screened a HeLa cell cDNA library with 1 of these cDNA fragments and isolated cDNAs encoding STK25, which they called YSK1. The predicted YSK1 protein contains an N-terminal kinase domain and lacks a putative Cdc42/Rac1-binding domain. Although the deduced kinase domain of YSK1 shows approximately 40% sequence identity to the kinase domains of yeast MAPKKKs, it is more similar to the kinase domains of Ste20-related kinases such as yeast Sps1, and human MST1 (604965) and GCK (603166). Recombinant YSK1 expressed in mammalian cells migrated as a 55-kD protein in SDS-polyacrylamide gels. Northern blot analysis of mouse tissues showed ubiquitous expression of Ysk1, with highest expression in brain and testis.
Pombo et al. (1996) found that human SOK1 was activated 2-fold by autophosphorylation and 3- to 7-fold by reactive oxygen intermediates. It was not activated by growth factors, alkylating agents, cytokines, or environmental stresses such as heat shock or osmolar stress.
Osada et al. (1997) showed that recombinant YSK1 had protein kinase activity in an in vitro assay. They found that overexpression of YSK1 does not lead to the activation of the ERK, JNK/SAPK, or p38/Mpk2 pathways.
Matsuki et al. (2010) noted that STK25 has a role in epithelial cell polarity, and they showed that it regulates neuronal cell polarity. Using overexpression and knockdown studies with cultured rat and mouse hippocampal and cortical neurons, Matsuki et al. (2010) found that a signaling pathway containing Stk25, Lkb1 (STK11; 602216), Strad (STRADA; 608626), and the Golgi protein Gm130 (GOLGA2; 602580) promoted Golgi condensation and multiple axon outgrowth while inhibiting Golgi deployment into dendrites and dendritic growth. This signaling pathway acted in opposition to the reelin (RELN; 600514)-Dab1 (603448) pathway, which tended to inhibit Golgi condensation and axon outgrowth and favor Golgi deployment into dendrites and dendrite outgrowth.
Gross (2014) mapped the STK25 gene to chromosome 2q37.3 based on an alignment of the STK25 sequence (GenBank BC091505) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 8/29/2014.
Matsuki, T., Matthews, R. T., Cooper, J. A., van der Brug, M. P., Cookson, M. R., Hardy, J. A., Olson, E. C., Howell, B. W. Reelin and Stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment. Cell 143: 826-836, 2010. [PubMed: 21111240] [Full Text: https://doi.org/10.1016/j.cell.2010.10.029]
Osada, S., Izawa, M., Saito, R., Mizuno, K., Suzuki, A., Hirai, S., Ohno, S. YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but is not involved in the known MAPK pathways. Oncogene 14: 2047-2057, 1997. [PubMed: 9160885] [Full Text: https://doi.org/10.1038/sj.onc.1201043]
Pombo, C. M., Bonventre, J. V., Molnar, A., Kyriakis, J., Force, T. Activation of a human Ste20-like kinase by oxidant stress defines a novel stress response pathway. EMBO J. 15: 4537-4546, 1996. [PubMed: 8887545]