Dataset Information

Lats2 modulates adipocyte proliferation and differentiation via hippo signaling.

ABSTRACT: First identified in Drosophila and highly conserved in mammals, the Hippo pathway controls organ size. Lats2 is one of the core kinases of the Hippo pathway and plays major roles in cell proliferation by interacting with the downstream transcriptional cofactors YAP and TAZ. Although the function of the Hippo pathway and Lats2 is relatively well understood in several tissues and organs, less is known about the function of Lats2 and Hippo signaling in adipose development. Here, we show that Lats2 is an important modulator of adipocyte proliferation and differentiation via Hippo signaling. Upon activation, Lats2 phosphorylates YAP and TAZ, leading to their retention in the cytoplasm, preventing them from activating the transcription factor TEAD in the nucleus. Because TAZ remains in the cytoplasm, PPAR? regains its transcriptional activity. Furthermore, cytoplasmic TAZ acts as an inhibitor of Wnt signaling by suppressing DVL2, thereby preventing ?-catenin from entering the nucleus to stimulate TCF/LEF transcriptional activity. The above effects contribute to the phenotype of repressed proliferation and accelerated differentiation in adipocytes. Thus, Lats2 regulates the balance between proliferation and differentiation during adipose development. Interestingly, our study provides evidence that Lats2 not only negatively modulates cell proliferation but also positively regulates cell differentiation.

SUBMITTER: An Y

PROVIDER: S-EPMC3745423 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Lats2 modulates adipocyte proliferation and differentiation via hippo signaling.

An Yang Y Kang Qianqian Q Zhao Yaofeng Y Hu Xiaoxiang X Li Ning N

PloS one 20130816 8

First identified in Drosophila and highly conserved in mammals, the Hippo pathway controls organ size. Lats2 is one of the core kinases of the Hippo pathway and plays major roles in cell proliferation by interacting with the downstream transcriptional cofactors YAP and TAZ. Although the function of the Hippo pathway and Lats2 is relatively well understood in several tissues and organs, less is known about the function of Lats2 and Hippo signaling in adipose development. Here, we show that Lats2 ...[more]

PMID: 23977200

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Project description:The Hippo signaling pathway is involved in the formation and development of the cardiovascular system. In the present study, the effects of WWC family member 3 (WWC3) on vascular smooth muscle cells (VSMCs) following injury were investigated, in addition to the associated mechanisms underlying this process. Platelet‑derived growth factor BB (PDGF‑BB) was used as a cell injury factor, and rats with balloon injuries were used as a model of carotid intimal injury. Furthermore, the expression levels of WWC3 in VSMCs and arteries post‑injury were investigated, in addition to the effect of WWC3 on the proliferation and migration of VSMCs. The results demonstrated that following injury, WWC3 expression was suppressed in VSMCs and the rat carotid artery, and the activity of the Hippo signaling pathway was significantly downregulated. In addition, the expression of YY1‑associated protein‑1 (YAP) and a number of its downstream target genes, including connective tissue growth factor (CTGF), were enhanced, thus enhancing the proliferation and migration of VSMCs. Knockdown of WWC3 suppressed the levels of large tumor suppressor kinase 1 (LATS1) expression and YAP phosphorylation, and the expression of YAP, CTGF and cyclin E was subsequently enhanced, thus promoting cell proliferation and migration. Similar results were obtained following overexpression of WWC3. Treatment with PDGF‑BB was revealed to suppress the proliferation and migration of VSMCs transfected with the WWC3 plasmid, compared with VSMCs transfected with an empty vector. The present study demonstrated that WWC3 may interact with LATS1 in order to upregulate the Hippo signaling pathway via co‑immunoprecipitation and enhancement of the phosphorylation of LATS1, in addition to the corresponding suppression of the nuclear import of YAP. However, VSMCs transfected with WWC3 plasmid with a deletion of the WW domain fail to exhibit this effect. These results suggested that WWC3 expression is downregulated in VSMCs during neointimal hyperplasia following injury (PDGF‑BB stimulation or balloon injury). WWC3 upregulates the activity of the Hippo signaling pathway, and weakens the proliferation and migration of VSMCs. Furthermore, the results of the present study suggested that WWC3 may interact with LATS1 to promote the phosphorylation of YAP and reduce its nuclear translocation, upregulate the activity of the Hippo pathway, and suppress the proliferation and migration of VSMCs following injury.

Dataset Information

Lats2 modulates adipocyte proliferation and differentiation via hippo signaling.

Publications

Lats2 modulates adipocyte proliferation and differentiation via hippo signaling.

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