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Article: Fyn-phosphorylated PIKE-A binds and inhibits AMPK signaling, blocking its tumor suppressive activity

TitleFyn-phosphorylated PIKE-A binds and inhibits AMPK signaling, blocking its tumor suppressive activity
Authors
Issue Date1-Jan-2016
PublisherSpringer Nature [academic journals on nature.com]
Citation
Cell Death & Differentiation, 2016, v. 23, n. 1, p. 52-63 How to Cite?
Abstract

The AMP-activated protein kinase, a key regulator of energy homeostasis, has a critical role in metabolic disorders and cancers. AMPK is mainly regulated by cellular AMP and phosphorylation by upstream kinases. Here, we show that PIKE-A binds to AMPK and blocks its tumor suppressive actions, which are mediated by tyrosine kinase Fyn. PIKE-A directly interacts with AMPK catalytic alpha subunit and impairs T172 phosphorylation, leading to repression of its kinase activity on the downstream targets. Mutation of Fyn phosphorylation sites on PIKE-A, depletion of Fyn, or pharmacological inhibition of Fyn blunts the association between PIKE-A and AMPK, resulting in loss of its inhibitory effect on AMPK. Cell proliferation and oncogenic assays demonstrate that PIKE-A antagonizes tumor suppressive actions of AMPK. In human glioblastoma samples, PIKE-A expression inversely correlates with the p-AMPK levels, supporting that PIKE-A negatively regulates AMPK activity in cancers. Thus, our findings provide additional layer of molecular regulation of the AMPK signaling pathway in cancer progression.


Persistent Identifierhttp://hdl.handle.net/10722/340484
ISSN
2023 Impact Factor: 13.7
2023 SCImago Journal Rankings: 4.102
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, S-
dc.contributor.authorQi, Q-
dc.contributor.authorChan, CB-
dc.contributor.authorZhou, W-
dc.contributor.authorChen, J-
dc.contributor.authorLuo, HR-
dc.contributor.authorAppin, C-
dc.contributor.authorBrat, DJ-
dc.contributor.authorYe, K-
dc.date.accessioned2024-03-11T10:44:59Z-
dc.date.available2024-03-11T10:44:59Z-
dc.date.issued2016-01-01-
dc.identifier.citationCell Death & Differentiation, 2016, v. 23, n. 1, p. 52-63-
dc.identifier.issn1350-9047-
dc.identifier.urihttp://hdl.handle.net/10722/340484-
dc.description.abstract<p>The AMP-activated protein kinase, a key regulator of energy homeostasis, has a critical role in metabolic disorders and cancers. AMPK is mainly regulated by cellular AMP and phosphorylation by upstream kinases. Here, we show that PIKE-A binds to AMPK and blocks its tumor suppressive actions, which are mediated by tyrosine kinase Fyn. PIKE-A directly interacts with AMPK catalytic alpha subunit and impairs T172 phosphorylation, leading to repression of its kinase activity on the downstream targets. Mutation of Fyn phosphorylation sites on PIKE-A, depletion of Fyn, or pharmacological inhibition of Fyn blunts the association between PIKE-A and AMPK, resulting in loss of its inhibitory effect on AMPK. Cell proliferation and oncogenic assays demonstrate that PIKE-A antagonizes tumor suppressive actions of AMPK. In human glioblastoma samples, PIKE-A expression inversely correlates with the p-AMPK levels, supporting that PIKE-A negatively regulates AMPK activity in cancers. Thus, our findings provide additional layer of molecular regulation of the AMPK signaling pathway in cancer progression.</p>-
dc.languageeng-
dc.publisherSpringer Nature [academic journals on nature.com]-
dc.relation.ispartofCell Death & Differentiation-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleFyn-phosphorylated PIKE-A binds and inhibits AMPK signaling, blocking its tumor suppressive activity-
dc.typeArticle-
dc.identifier.doi10.1038/cdd.2015.66-
dc.identifier.scopuseid_2-s2.0-84949539395-
dc.identifier.volume23-
dc.identifier.issue1-
dc.identifier.spage52-
dc.identifier.epage63-
dc.identifier.eissn1476-5403-
dc.identifier.isiWOS:000368062000015-
dc.identifier.issnl1350-9047-

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