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serine/threonine kinase 3 OKDB#: 3785
 Symbols: STK3 Species: human
 Synonyms: KRS1, MST2  Locus: 8q22.2 in Homo sapiens

For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment NCBI Summary: This gene encodes a serine/threonine protein kinase activated by proapoptotic molecules indicating the encoded protein functions as a growth suppressor. Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
General function Intracellular signaling cascade, Enzyme
Cellular localization Cytoplasmic
Ovarian function Primary follicle growth, Preantral follicle growth, Antral follicle growth, Oocyte maturation
Comment Lats1 Deletion Causes Increased Germ Cell Apoptosis and Follicular Cysts in Mouse Ovaries. Sun T et al. (2015) The hippo signaling pathway is essential for regulating proliferation and apoptosis in mammalian cells. The LATS1 kinase is a core member of the hippo signaling pathway that phosphorylates and inactivates the transcriptional co-activators YAP1 and WWTR1. Deletion of Lats1 results in low neonate survival and ovarian stromal tumors in surviving adults, but the effects of Lats1 on early follicular development are not understood. Here, the expression of hippo pathway components were including Wwtr1, Stk4, Stk3, Lats2 and Yap1 transcripts were decreased by 50% in mouse ovaries between 2 and 8 days of age while expression was maintained from 8 days to 21 days and after priming with eCG. LATS1, LATS2, and MOB1B were localized to both germ and somatic cells of primordial to antral follicles. Interestingly, YAP1 was predominantly cytoplasmic, while WWTR1 was nuclear in oocytes and somatic cells. Deletion of Lats1 caused an increase in germ cell apoptosis from 1.7% in control ovaries to 3.6% in Lats1 mutant ovaries and a 58% and 32% decrease in primordial and activated follicle numbers in cultured mutant ovaries. Surprisingly, there was an increase in Bmp15, but not Gdf9, Figla, Nobox transcripts or somatic-specific transcripts Amh and Wnt4 in cultured Lats1 mutant ovaries. Lastly, Lats1 mutant ovaries developed ovarian cysts at a higher frequency (43%) compared to heterozygous (24%) and control ovaries (8%). The results show that the hippo pathway is active in ovarian follicles and that LATS1 is required to maintain the pool of germ cells and primordial follicles.////////////////// Antibody Microarray Analyses of Signal Transduction Protein Expression and Phosphorylation during Porcine Oocyte Maturation. Pelech S et al. Kinex antibody microarray analyses was used to investigate the regulation of 188 protein kinases, 24 protein phosphatases, and 170 other regulatory proteins during meiotic maturation of immature germinal vesicle (GV+) pig oocytes to maturing oocytes that had completed meiosis I (MI), and fully mature oocytes arrested at metaphase of meiosis II (MII). Increases in apparent protein levels of protein kinases accounted for most of the detected changes during the GV to MI transition, whereas reduced protein kinase levels and increased protein phosphorylation characterized the MI to MII transition. During the MI to MII period, many of the MI-associated increased levels of the proteins and phosphosites were completely or partially reversed. The regulation of these proteins were also examined in parallel during the meiotic maturation of bovine, frog, and sea star oocytes with the Kinex antibody microarray. Western blotting analyses confirmed altered expression levels of Bub1A, IRAK4, MST2, PP4C, and Rsk2, and the phosphorylation site changes in the kinases Erk5 (T218 + Y220), FAK (S722), GSK3-beta (Y216), MEK1 (S217 + S221) and PKR1 (T451), and nucleophosmin/B23 (S4) during pig oocyte maturation.
Expression regulated by
Ovarian localization Oocyte, Granulosa, Theca
Comment Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Kawamura K 2013 et al. Primary ovarian insufficiency (POI) and polycystic ovarian syndrome are ovarian diseases causing infertility. Although there is no effective treatment for POI, therapies for polycystic ovarian syndrome include ovarian wedge resection or laser drilling to induce follicle growth. Underlying mechanisms for these disruptive procedures are unclear. Here, we explored the role of the conserved Hippo signaling pathway that serves to maintain optimal size across organs and species. We found that fragmentation of murine ovaries promoted actin polymerization and disrupted ovarian Hippo signaling, leading to increased expression of downstream growth factors, promotion of follicle growth, and the generation of mature oocytes. In addition to elucidating mechanisms underlying follicle growth elicited by ovarian damage, we further demonstrated additive follicle growth when ovarian fragmentation was combined with Akt stimulator treatments. We then extended results to treatment of infertility in POI patients via disruption of Hippo signaling by fragmenting ovaries followed by Akt stimulator treatment and autografting. We successfully promoted follicle growth, retrieved mature oocytes, and performed in vitro fertilization. Following embryo transfer, a healthy baby was delivered. The ovarian fragmentation-in vitro activation approach is not only valuable for treating infertility of POI patients but could also be useful for middle-aged infertile women, cancer patients undergoing sterilizing treatments, and other conditions of diminished ovarian reserve. MST2was expressed in day 10 ovaries at levels higher than MST1 /////////////////////////
Follicle stages Primary, Secondary, Antral
Mutations 0 mutations
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created: May 22, 2008, 1:07 p.m. by: hsueh   email:
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last update: Aug. 1, 2017, 1:48 p.m. by: hsueh    email:

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