YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1, but is not involved in the known MAPK pathways

Abstract

To clarify the upstream regulatory mechanism of mitogen-activated protein kinase (MAPK), we performed the reverse transcriptase-based polymerase chain reaction (RT ± PCR) with degenerate primers synthesized based on sequences conserved among the kinase domains of yeast MAPK kinase kinases (MAPKKKs), Ste11, Bck1, and Byr2. We isolated several mammalian cDNA fragments that encode kinase subdomains sharing signi®cant sequence homology with yeast MAPKKKs. Subsequent screening of a HeLa cell cDNA library using one of these cDNA fragments as a probe resulted in the isolation of a full-length cDNA that encodes a novel protein kinase. The catalytic domain sequence of this gene product is closely related to those of budding yeast Sps1 and Ste20 protein kinases. Thus, we call this protein YSK1 (Yeast Sps1/Ste20-related Kinase 1). The transcript of YSK1 was detected in a wide range of tissues and cells. Immunoprecipitated YSK1 shows protein kinase activity. Although YSK1 is signi®cantly similar in its kinase domain to kinases of the yeast and mammalian MAPK pathways, the overexpression of YSK1 did not lead to the activation of the ERK (extracellular signal-regulated kinase) pathway, JNK (c-Jun NH 2 -terminal kinase)/SAPK (stress-activated protein kinase) pathway, or p38/Mpk2 pathway. These results suggest that YSK1 may be involved in the regulation of a novel intracellular signaling pathway.

Serine/threonine protein kinase 25 (STK25): a novel negative regulator of lipid and glucose metabolism in rodent and human skeletal muscle

“…1a). Similarly to previous reports in which mRNA levels of Stk25 in rodents were assessed by northern blot [3,4], Stk25 was identified in all tissues examined. In both mouse and rat tissues, the mRNA expression was highest in the small and large intestine and the brain, compared with heart, skeletal muscle, spleen, liver, lung, kidney and adipose tissues.…”

“…STK25 has been shown to be slightly activated by reactive oxygen intermediates but not by growth factors or other environmental stresses, such as heat shock or osmolar stress [3]. Interestingly, STK25 does not activate any of the known MAPK pathways [3,4] and thus this kinase might be involved in the regulation of a novel intracellular signalling pathway. Recently, STK25 was shown to be involved in two cellular processes: regulation of cell migration and modulation of cell death.…”

Cloning of MASK, a Novel Member of the Mammalian Germinal Center Kinase III Subfamily, with Apoptosis-inducing Properties

“…One of the most crucial subjects in the study of the mammalian GCK family kinases in the post-genome era is to establish distinct features of a kinase in reference to the other members in the same subfamily and to kinases in different subfamilies. In this sense, the most peculiar subfamily may be the GCK-III subfamily consisting of two mammalian kinases, SOK1/YSK1 and Mst3, and their Drosophila and C. elegans orthologs, CG5169 and T19A5.2 (1,(5)(6)(7). Unlike other GCK family kinases, neither SOK1/YSK1 nor Mst3 has been shown to activate JNK or p38 MAPK pathways (5-7).…”

The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins

“…GLK (GCK-like kinase), a very recently cloned kinase (Diener et al, 1997), which has not been analysed in this study, also contains such a motif, while no potential Crk or CRKL SH3(1) binding motifs are obvious in the related germinal centre kinase GCK (Katz et al, 1994). Interestingly, the also homologous human kinase YSK1 (Osada et al, 1997) contains a similar motif (PAEPVK), while the virtually identical human kinase SOK1 (Pombo et al, 1996) diers in the corresponding sequence in a position expected to be crucial for potential SH3 binding (PADAVK).…”