Abstract：
:By controlling the YAP1 proto-oncoprotein Hippo signalling plays important roles in cancer-associated processes. Current evidence suggests that the Hippo kinases MST1/2 together with the MOB1 scaffold protein promote the formation of active MOB1/LATS complexes which phosphorylate and thereby inhibit YAP1. However, the regulatory mechanisms of MST1/2-MOB1-LATS signalling are currently underinvestigated. Therefore, we studied LATS2 variants carrying specific modifications that mimic gain or loss of phosphorylation and/or abolish MOB1/LATS2 interactions. We discovered that Ser872 T-loop and Thr1041 hydrophobic motif (HM) phosphorylation of LATS2 is essential for LATS2 activation. MST1/2 phosphorylate LATS2 on Thr1041, but not Ser872, while MOB1 binding to LATS2 supports both phosphorylation events. Significantly, LATS2-PIF, a LATS2 variant containing the PRK2 HM, acts as a hyperactive LATS2 kinase that efficiently phosphorylates YAP1 and inhibits the transcriptional co-activity of YAP1. This inhibitory function of LATS2-PIF is dependent on LATS2 kinase activity, while MOB1/LATS2 and YAP1/LATS2 complex formation is dispensable, suggesting that elevated LATS2 kinase activity can be sufficient to oppose YAP1. Taken together, our characterisation of LATS2 variants uncovers novel insights into the regulation of LATS kinases in Hippo signalling.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Hoa L,Kulaberoglu Y,Gundogdu R,Cook D,Mavis M,Gomez M,Gomez V,Hergovich Adoi
10.1016/j.cellsig.2016.02.012subject
Has Abstractpub_date
2016-05-01 00:00:00pages
488-497issue
5eissn
0898-6568issn
1873-3913pii
S0898-6568(16)30037-7journal_volume
28pub_type
杂志文章abstract：:Regulators of G protein signalling (RGS) proteins are united into a family by the presence of the RGS domain which serves as a GTPase-activating protein (GAP) for various Galpha subunits of heterotrimeric G proteins. Through this mechanism, RGS proteins regulate signalling of numerous G protein-coupled receptors. In a...
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pub_type： 杂志文章
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更新日期：2020-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.03.014
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
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更新日期：2016-02-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2018-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2011.12.001
更新日期：2012-04-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0898-6568(94)90062-0
更新日期：1994-01-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2009.07.018
更新日期：2009-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.02.006
更新日期：2014-06-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2018.08.009
更新日期：2018-11-01 00:00:00
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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
doi：10.1016/j.cellsig.2011.09.022
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pub_type： 杂志文章
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更新日期：2020-02-01 00:00:00
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doi：10.1016/j.cellsig.2005.08.020
更新日期：2006-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0898-6568(93)90038-n
更新日期：1993-11-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
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更新日期：2014-09-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/j.cellsig.2005.11.001
更新日期：2006-09-01 00:00:00
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pub_type： 杂志文章,评审
doi：10.1016/0898-6568(95)00024-j
更新日期：1995-08-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2014.08.028
更新日期：2014-12-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/j.cellsig.2015.01.012
更新日期：2015-04-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/0898-6568(94)90037-x
更新日期：1994-03-01 00:00:00
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journal_title：Cellular signalling
pub_type： 杂志文章
doi：10.1016/s0898-6568(03)00014-7
更新日期：2003-08-01 00:00:00
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journal_title：Cellular signalling
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doi：10.1016/j.cellsig.2004.06.004
更新日期：2005-01-01 00:00:00
