NCBI Summary:
This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]
General function
Enzyme
Comment
Cellular localization
Cytoplasmic
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Ovarian function
Steroid metabolism
Comment
Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) mediates the LH-induced stimulation of progesterone synthesis in the porcine corpus luteum. Zhang D et al. (2019) Progesterone (P4) synthesized by the corpus luteum (CL) plays a key role in the establishment and maintenance of pregnancy. The LH signal is important for luteinisation and P4 synthesis in pigs. In a previous study, we demonstrated that mitogen-activated protein kinase kinase kinase 8 (MAP3K8) regulates P4 synthesis in mouse CL, but whether the function and mechanism of MAP3K8 in the pig is similar to that in the mouse is not known. Thus, in the present study we investigated the effects of MAP3K8 on porcine CL. Abundant expression of MAP3K8 was detected in porcine CL, and, in pigs, MAP3K8 expression was higher in mature CLs (or those of the mid-luteal phase) than in regressing CLs (late luteal phase). Further functional studies in cultured porcine luteal cells showed that P4 synthesis and the expression of genes encoding the key enzymes in P4 synthesis are significantly reduced when MAP3K8 is inhibited with the MAP3K8 inhibitor Tpl2 kinase inhibitor (MAP3K8i, 10μM). After 12-24h treatment of luteal cells with 100ngmL-1 LH, MAP3K8 expression and P4 secretion were significantly upregulated. In addition, the 10μM MAP3K8 inhibitor blocked the stimulatory effect of LH on P4 synthesis and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in porcine luteal cells. The LH-induced increases in MAP3K8 phosphorylation and expression, ERK1/2 phosphorylation and P4 synthesis were all blocked when protein kinase A was inhibited by its inhibitor H89 (20 μM) in porcine luteal cells. In conclusion, MAP3K8 mediates the LH-induced stimulation of P4 synthesis through the PKA/mitogen-activated protein kinase signalling pathway in porcine CL.//////////////////
Mitogen-activated protein kinase 8 (MAP3K8) mediates the signaling pathway of estradiol stimulating progesterone production through G protein-coupled receptor 30 (GPR30) in mouse Corpus luteum. Liu Y et al. (2015) The corpus luteum (CL) is a transient endocrine gland developed from the ovulated follicles, and the most important function is to synthesize and secrete progesterone (P4), a key hormone to maintain normal pregnancy and estrus cycle in most mammals. It is known that estrogen has a vital role in stimulating P4 synthesis in CL, but it still remains unclear about the mechanism of estrodiol (E2) regulating P4 production in CL. Our results here firstly show that all of the CL cells express Mitogen-activated Protein Kinase 8 (MAP3K8) and MAP3K8 level is much higher at mid-stage than at early and late stages during CL development. The further functional studies show that the forced inhibition of endogenous MAP3K8 by using MAP3K8-siRNA and MAP3K8 signaling inhibitor (MAP3K8i) in the luteal cells significantly block the P4 synthesis and neutralize the enhancing effect of E2 on P4 production in the CL. In addition, our results here demonstrate that the stimulating effect of E2 on P4 synthesis relies on the estrogen no-classical protein-coupled receptor 30 (GPR30) and MAP3K8 is involved in mediating the GPR30 signaling of E2 affecting P4 synthesis via stimulating ERK phosphorylation. These novel findings are critical for our understanding the ovary physiology and pathological mechanism.//////////////////
Expression regulated by
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Ovarian localization
Cumulus, Luteal cells
Comment
Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients. Huang X et al. (2016) Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women and is characterised by polycystic ovaries, hyperandrogenism, and chronic anovulation. Although the clinical and biochemical signs of PCOS are typically heterogeneous, abnormal folliculogenesis is considered a common characteristic of PCOS. Our aim was to identify the altered miRNA and mRNA expression profiles in the cumulus cells of PCOS patients to research their molecular function in the aetiology and pathophysiology of PCOS. In the present study, the miRNA expression profiles of the cumulus cell samples isolated from five PCOS and five control patients were determined by a miRNA microarray. At the same time, the altered mRNA profiles of the same cumulus cells samples were also identified by a cDNA microarray. From the microarrays data, 17 miRNAs and 1263 mRNAs showed significantly different expression in the PCOS cumulus cells. The differentially expressed miRNA-509-3p and its potential target gene (MAP3K8) were identified from the miRNA and mRNA microarrays, respectively. The expression of miR-509-3p was up-regulated, and MAP3K8 was down-regulated, in the PCOS cumulus cells. The direct interaction between miR-509-3p and MAP3K8 was confirmed by a luciferase activity assay in KGN cells. In addition, miR-509-3p mimics or inhibitor transfection tests in KGN cells further confirmed that miR-509-3p improved E2 secretion by inhibiting the expression of MAP3K8. These results help to characterise the pathogenesis of anovulation in PCOS, especially the regulation of oestradiol production.//////////////////