MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Meng Z et al. (2015) The Hippo pathway plays a central role in tissue homoeostasis, and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include a kinase cascade of MST1/2 and LATS1/2 and the transcription co-activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have identified MAP4K family members-Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined deletion of MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results demonstrate that MAP4Ks act in parallel to and are partially redundant with MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as components of the expanded Hippo pathway.//////////////////
NCBI Summary:
Germinal center kinases (GCKs), such as TNIK, are characterized by an N-terminal kinase domain and a C-terminal GCK domain that serves a regulatory function (Fu et al., 1999 [PubMed 10521462]).[supplied by OMIM, Mar 2008]
General function
Intracellular signaling cascade, Enzyme
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Cellular localization
Cytoplasmic
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Ovarian function
Oocyte maturation
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Expression regulated by
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Ovarian localization
Cumulus
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Differences in the transcriptional profiles of human cumulus cells isolated from MI and MII oocytes of patients with polycystic ovary syndrome (PCOS). Huang X et al. Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. Abnormalities of endocrine and intra-ovarian paracrine interactions may change the microenvironment for oocyte development during the folliculogenesis process and reduced oocyte development competence in PCOS patients who are sufferring from anovulatory infertility and pregnancy loss. In this microenvironment, the cross talk between the oocyte and surrounding cumulus cells (CCs) is critical for obtaining oocyte competence. The aim of our study was to investigate gene expression profile of CCs from PCOS patients undergoing IVF cycles in terms of oocyte maturity by using human Genome U133 Plus 2.0 microarrays. A total of 59 genes were differentially expressed between the two CC categories. Most of these genes were identified to be involved in one or more of the following pathways: receptor interactions, calcium signaling, metabolism and biosynthesis, focal adhesion, melanogenesis, leukocyte transendothelial migration, Wnt signaling pathway, and Type II diabetes mellitus. According to the different expression levels in the microarray and their putative functions, six differentially expressed genes (LHCGR, ANGPTL1, TNIK, GRIN2A, SFRP4 and SOCS3) were selected and analyzed by quantitative RT-PCR. The qRT-PCR results were consistent with the microarray data. Moreover, the molecular signatures (LHCGR, TNIK and SOCS3) were associated with developmental potential from embryo to blastocyst stage and were proposed as biomarkers for embryo viability in PCOS patients. Our results may have important clinically useful by offering a new potential strategy for competent oocyte/embryo selection in PCOS patients.