scholarly journals The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1

Cell Research ◽  
2015 ◽  
Vol 25 (12) ◽  
pp. 1299-1313 ◽  
Author(s):  
Carsten Gram Hansen ◽  
Yuen Lam Dora Ng ◽  
Wai-Ling Macrina Lam ◽  
Steven W Plouffe ◽  
Kun-Liang Guan
Keyword(s):  
Amino Acid ◽  
Cell Growth ◽  
Hippo Pathway ◽  
The Hippo Pathway ◽  
Amino Acid Signaling

scholarly journals Staurosporine targets the Hippo pathway to inhibit cell growth

2018 ◽  
Vol 10 (3) ◽  
pp. 267-269
Author(s):  
Xueyan Ma ◽  
Peixue Li ◽  
Peihao Chen ◽  
Jinhui Li ◽  
Hongling Huang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Hippo Pathway ◽  
Inhibit Cell Growth ◽  
The Hippo Pathway

scholarly journals RASSF effectors couple diverse RAS subfamily GTPases to the Hippo pathway

2020 ◽  
Author(s):  
Dhanaraman Thillaivillalan ◽  
Swati Singh ◽  
Ryan C. Killoran ◽  
Anamika Singh ◽  
Xingjian Xu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nuclear Localization ◽  
Hippo Pathway ◽  
Effector Proteins ◽  
Amino Acid Substitutions ◽  
Structural Modelling ◽  
Ras Proteins ◽  
Domain Family ◽  
Ras Gtpases ◽  
The Hippo Pathway

AbstractActivated RAS GTPases signal by directly binding effector proteins. Effectors have a folded RAS association (RA) domain that binds exclusively to GTP-loaded RAS, but the specificity of most RA domains for >150 RAS superfamily GTPases is unknown. Ten RAS-association domain family (RASSF) proteins comprise the largest group of effectors, proposed to couple RAS to the pro-apoptotic Hippo pathway. We show that RASSF1-6 complex with Hippo kinase, while RASSF7-10 are a separate family related to p53-regulatory ASPP effectors. Only RASSF5 directly binds activated HRAS and KRAS. Structural modelling reveals that expansion of RASSFs in vertebrates included amino acid substitutions that alter their GTPase binding specificity. We demonstrate that the tumour suppressor RASSF1A complexes with the GTPases GEM, REM1, REM2 and the enigmatic RASL12. Interplay between RASSFs and RAS GTPases can drastically restrict YAP1 nuclear localization. Thus, these simple scaffolds can link activation of diverse RAS proteins to Hippo or p53 regulation.

scholarly journals GATOR2 complex–mediated amino acid signaling regulates brain myelination

2022 ◽  
Vol 119 (3) ◽  
pp. e2110917119
Author(s):  
Zongyan Yu ◽  
Zhiwen Yang ◽  
Guoru Ren ◽  
Yingjie Wang ◽  
Xiang Luo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Growth Factor ◽  
Cell Growth ◽  
Brain Development ◽  
Cell Cycle Progression ◽  
Growth Factor Signaling ◽  
Organ Development ◽  
Signaling Complex ◽  
Amino Acid Signaling

Amino acids are essential for cell growth and metabolism. Amino acid and growth factor signaling pathways coordinately regulate the mechanistic target of rapamycin complex 1 (mTORC1) kinase in cell growth and organ development. While major components of amino acid signaling mechanisms have been identified, their biological functions in organ development are unclear. We aimed to understand the functions of the critically positioned amino acid signaling complex GAP activity towards Rags 2 (GATOR2) in brain development. GATOR2 mediates amino acid signaling to mTORC1 by directly linking the amino acid sensors for arginine and leucine to downstream signaling complexes. Now, we report a role of GATOR2 in oligodendrocyte myelination in postnatal brain development. We show that the disruption of GATOR2 complex by genetic deletion of meiosis regulator for oocyte development (Mios, encoding a component of GATOR2) selectively impairs the formation of myelinating oligodendrocytes, thus brain myelination, without apparent effects on the formation of neurons and astrocytes. The loss of Mios impairs cell cycle progression of oligodendrocyte precursor cells, leading to their reduced proliferation and differentiation. Mios deletion manifests a cell type–dependent effect on mTORC1 in the brain, with oligodendroglial mTORC1 selectively affected. However, the role of Mios/GATOR2 in oligodendrocyte formation and myelination involves mTORC1-independent function. This study suggests that GATOR2 coordinates amino acid and growth factor signaling to regulate oligodendrocyte myelination.

scholarly journals Fission yeast polycystin Pkd2p promotes transition to cell growth during cytokinesis

2021 ◽  
Author(s):  
Debatrayee Sinha ◽  
Denisa Ivan ◽  
Ellie Gibbs ◽  
Madhurya Chetluru ◽  
John W Goss ◽  
...  
Keyword(s):  
Cell Growth ◽  
Fission Yeast ◽  
Genetic Disorders ◽  
Hippo Pathway ◽  
Cell Stiffness ◽  
Growth Defect ◽  
Temperature Sensitive ◽  
Size Growth ◽  
Autosomal Dominant Polycystic Kidney ◽  
The Hippo Pathway

Polycystins are evolutionally conserved cation channels. Mutations of human polycystins lead to one of the most common genetic disorders, Autosomal Dominant Polycystic Kidney Disorder. Interestingly, the fission yeast homologue Pkd2p is required for cytokinesis the last stage of cell division, but the mechanism remains unclear. Motivated by our discovery of the epistatic genetic interactions between pkd2 and the Hippo pathway Septation Initiation Network (SIN), we investigated their interplay during cytokinesis. We found that pkd2 modulated the localization as well as the activities of SIN. Most notably, pkd2 promotes a transition to cell size growth during cytokinesis, opposed by SIN. The role of Pkd2p in cell growth is not limited to cytokinesis. A newly isolated pkd2 temperature-sensitive mutant largely blocked the tip expansion of cells during interphase. Such growth defect was accompanied by frequent shrinking, reduced cell volume, and decreased cell stiffness. We conclude that Pkd2p promotes transition to the post-mitosis cell growth in coordination with the Hippo pathway

scholarly journals Regulation of Myocardial Cell Growth and Death by the Hippo Pathway

2016 ◽  
Vol 80 (7) ◽  
pp. 1511-1519 ◽  
Author(s):  
Shohei Ikeda ◽  
Junichi Sadoshima
Keyword(s):  
Cell Growth ◽  
Hippo Pathway ◽  
Myocardial Cell ◽  
The Hippo Pathway
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