Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue.
The Ste20 family of serine/threonine kinases plays an important role in numerous cellular functions such as growth, apoptosis, and morphogenesis. We have identified a previously cloned but uncharacterized family member termed Stk10, which is a human homolog of murine Lok, a serine/threonine kinase highly expressed in lymphocytes. Northern analysis demonstrated that the Stk10 transcript is present in many tissues, although highest expression levels are seen in hematopoietic cells. Due to close sequence homology to human Slk and Xenopus laevis xPlkk1, two polo-like kinase kinases, we investigated whether Stk10 might also play a role as a Plk1 activator. Plk1 has been shown to be overexpressed in multiple tumor types, thus attracting high interest to its potential upstream regulators. We show here that Stk10 can associate with Plk1 in cells and furthermore can phosphorylate Plk1 in vitro. Engineered NIH-3T3 cell lines that overexpress a dominant negative version of Stk10 display an altered cell cycle phenotype characterized by increased DNA content, raising the possibility that expression of a dominant negative Stk10 may impinge upon Plk1 function in vivo; it has previously been shown that unregulated expression of Plk1 can result in a variety of nuclear defects. We suggest, therefore, that Stk10 is a novel polo-like kinase kinase that cooperates with hSlk to regulate Plk1 function in human cells.
Walter
Sarah A
SA
Department of Research, SUGEN Inc., South San Francisco, California 94080, USA. sarah-walter@sugen.com
Cutler
Richard E
RE
Martinez
Ricardo
R
Gishizky
Mikhail
M
Hill
Ronald J
RJ
D016475:3T3 Cells; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014981:Xenopus; D014982:Xenopus laevis; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D004247:DNA; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C474806:STK10 protein, human