Abstract：
:Glycogen synthase kinase 3beta (GSK3beta) is implicated in many biological events, including embryonic development, cell differentiation, apoptosis, and the insulin response. GSK3beta also plays a key role in the Wnt/beta-catenin pathway. The master regulator of the pigmentation microphthalmia-associated transcription factor (MITF) is a target for the Wnt pathway, however, to date, the regulatory role of GSK3beta in the control of melanogenesis has not been elucidated. In this study, we evaluated the effect of inhibiting GSK3beta activity on the regulation of melanocyte differentiation. Exposure of the murine melanoma cell line B16 and normal human melanocytes to GSK3beta specific inhibitors (SB216763, SB415286, BIO, and LiCl) resulted in a dose-dependent accumulation of beta-catenin. This is associated with the induction of melanocyte differentiation-associated markers such as melanin synthesis, tyrosinase activity, and expression of tyrosinase and the microphthalmia-associated transcription factor. Attenuation of GSK3beta activity has an inhibitory effect on cell growth, and this was accompanied by morphological changes. Moreover, treatment of B16 cells with a siRNA targeted against beta-catenin completely abolished the promelanogenic effect of GSK3beta inhibition, however, the overexpression of a constitutively active mutant form of beta-catenin (pCS2beta-cat-mut) only slightly increased the degree of pigmentation. These results demonstrated that GSK3beta is implicated in the regulation of melanogenesis and that pharmacological inhibition of its activity could increase melanin synthesis through mechanisms probably not restricted to Wnt/beta-catenin pathway activation.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Bellei B,Flori E,Izzo E,Maresca V,Picardo Mdoi
10.1016/j.cellsig.2008.06.001subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1750-61issue
10eissn
0898-6568issn
1873-3913pii
S0898-6568(08)00163-0journal_volume
20pub_type
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journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
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pub_type： 杂志文章
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(96)00101-5
更新日期：1996-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.06.001
更新日期：2006-05-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.109502
更新日期：2020-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2003.12.004
更新日期：2004-07-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.11.008
更新日期：2016-02-01 00:00:00
abstract：:IFN-gamma and TNF-alpha are major proinflammatory cytokines implicated in islet beta-cell destruction, which results in type-1 diabetes; however, the underlying mechanism is not clear. Using pancreatic beta-cell line MIN6N8 cells, co-treatment with TNF-alpha and IFN-gamma, but neither cytokine alone, synergistically i...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.03.020
更新日期：2005-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2008.05.017
更新日期：2008-10-01 00:00:00
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journal_title：Cellular signalling
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2013.08.012
更新日期：2014-01-01 00:00:00
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pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2005.11.003
更新日期：2006-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.03.010
更新日期：2014-07-01 00:00:00
abstract：:Interleukin-6-type cytokine receptors are expressed in polarized cells such as hepatocytes and intestinal cells. For the interleukin-6-receptor gp80 and its signal transducer gp130, a preferential basolateral localization was demonstrated in Madin-Darby canine kidney (MDCK) cells and two basolateral sorting signals we...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.09.006
更新日期：2006-08-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.09.017
更新日期：2014-12-01 00:00:00
abstract：:A reduced capacity for insulin to elicit increases in glucose uptake and metabolism in target tissues such as skeletal muscle is a common feature of obesity and diabetes. The association between lipid oversupply and such insulin resistance is well established, and evidence for mechanisms through which lipids could pla...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/s0898-6568(00)00110-8
更新日期：2000-10-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109877
更新日期：2021-02-01 00:00:00
abstract：:Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A(PKA) is considered to be a physiologic modulator of superoxide generation by stimulated neutrophils. Mechanisms of the inhibitory action of PKA are poorly understood. In this study, we investigated effects of cAMP-elevating agents on the phosphorylation ...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(96)00052-6
更新日期：1996-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(02)00017-7
更新日期：2002-09-01 00:00:00
abstract：BACKGROUND:Some microRNAs (miRNAs) are involved in osteogenic differentiation. In recent years, increasing evidences have revealed that exosomes contain specific miRNAs. However, the effect and mechanism of miR-23a-5p-containing exosomes in osteoblast remain largely unclear. METHODS:We extracted exosomes from RANKL-in...
journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2019.109504
更新日期：2020-06-01 00:00:00
abstract：:Neutrophils are key effector cells of the innate immune system, serving as a first line of defense in the response to injury and playing essential roles in the wound healing process. Following myocardial infarction (MI), neutrophils infiltrate into the infarct region to propagate inflammation and begin the initial pha...
journal_title：Cellular signalling
pub_type： 杂志文章,评审
doi：10.1016/j.cellsig.2020.109816
更新日期：2021-01-01 00:00:00
