STIM2 interacts with AMPK and regulates calcium-induced AMPK activation

Anoop Singh Chauhan; Xiaoguang Liu; Ji Jing; Hyemin Lee; Raj Kumar Yadav; Jindou Liu; Yubin Zhou; Boyi Gan

doi:10.1096/fj.201801225R

STIM2 interacts with AMPK and regulates calcium-induced AMPK activation

Anoop Singh Chauhan, Xiaoguang Liu, Ji Jing, Hyemin Lee, Raj Kumar Yadav, Jindou Liu, Yubin Zhou, Boyi Gan

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

AMPKis a crucial regulator of energyhomeostasis that acts downstream of its upstream kinase liver kinaseB1 (LKB1) and calcium/calmodulin-dependent protein kinase 2 (CaMKK2). LKB1 primarily phosphorylates AMPK after energy stress,whereas calcium-mediated activation ofAMPKrequiresCaMKK2, although the regulatorymechanisms of calcium-mediated AMPK activation remain unclear. Using biochemical, microscopic, and genetic approaches, we demonstrate that the stromal interaction molecule (STIM)2, a calcium sensor, acts as a novel regulator of CaMKK2-AMPK signaling.Wereveal that STIM2 interacts withAMPKand CaMKK2 and that the increase in intracellular calcium levels promotesAMPKcolocalization and interactionwith STIM2.We further show that STIM2 deficiency attenuates calciuminduced but not energy stress-induced AMPK activation, possibly by regulating the CaMKK2-AMPK interaction. Together, our results identify a previously unappreciated mechanism that modulates calcium-mediated AMPK activation.

Original language	English (US)
Pages (from-to)	2957-2970
Number of pages	14
Journal	FASEB Journal
Volume	33
Issue number	2
DOIs	https://doi.org/10.1096/fj.201801225R
State	Published - 2019

Keywords

CaMKK2
Energy stress
LKB1
STIM1

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Genetics

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Flow Cytometry and Cellular Imaging Facility
Functional Genomics Core
Cytogenetics and Cell Authentication Core

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10.1096/fj.201801225R

Cite this

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title = "STIM2 interacts with AMPK and regulates calcium-induced AMPK activation",

abstract = "AMPKis a crucial regulator of energyhomeostasis that acts downstream of its upstream kinase liver kinaseB1 (LKB1) and calcium/calmodulin-dependent protein kinase 2 (CaMKK2). LKB1 primarily phosphorylates AMPK after energy stress,whereas calcium-mediated activation ofAMPKrequiresCaMKK2, although the regulatorymechanisms of calcium-mediated AMPK activation remain unclear. Using biochemical, microscopic, and genetic approaches, we demonstrate that the stromal interaction molecule (STIM)2, a calcium sensor, acts as a novel regulator of CaMKK2-AMPK signaling.Wereveal that STIM2 interacts withAMPKand CaMKK2 and that the increase in intracellular calcium levels promotesAMPKcolocalization and interactionwith STIM2.We further show that STIM2 deficiency attenuates calciuminduced but not energy stress-induced AMPK activation, possibly by regulating the CaMKK2-AMPK interaction. Together, our results identify a previously unappreciated mechanism that modulates calcium-mediated AMPK activation.",

keywords = "CaMKK2, Energy stress, LKB1, STIM1",

author = "Chauhan, {Anoop Singh} and Xiaoguang Liu and Ji Jing and Hyemin Lee and Yadav, {Raj Kumar} and Jindou Liu and Yubin Zhou and Boyi Gan",

note = "Funding Information: The authors thank all members of the B.G. laboratory for their advice and technical assistance. This research was supported by the Andrew Sabin Family Fellow Award, the Sister Institution Network Fund, the Anna Fuller Fund, U.S. National Institutes of Health (NIH) National Cancer Institute Grant CA181196 (to B.G.), NIH National Institute of General Medical Sciences Grant R01GM112003, Welch Foundation Grant BE-1913, American Cancer Society Grant RSG-16-215-01 TBE (to Y.Z.), and NIH Cancer Center Support Grant P30CA016672 to The University of Texas M. D. Anderson Cancer Center. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2019 The Author(s).",

year = "2019",

doi = "10.1096/fj.201801225R",

language = "English (US)",

volume = "33",

pages = "2957--2970",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "2",

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TY - JOUR

T1 - STIM2 interacts with AMPK and regulates calcium-induced AMPK activation

AU - Chauhan, Anoop Singh

AU - Liu, Xiaoguang

AU - Jing, Ji

AU - Lee, Hyemin

AU - Yadav, Raj Kumar

AU - Liu, Jindou

AU - Zhou, Yubin

AU - Gan, Boyi

N1 - Funding Information: The authors thank all members of the B.G. laboratory for their advice and technical assistance. This research was supported by the Andrew Sabin Family Fellow Award, the Sister Institution Network Fund, the Anna Fuller Fund, U.S. National Institutes of Health (NIH) National Cancer Institute Grant CA181196 (to B.G.), NIH National Institute of General Medical Sciences Grant R01GM112003, Welch Foundation Grant BE-1913, American Cancer Society Grant RSG-16-215-01 TBE (to Y.Z.), and NIH Cancer Center Support Grant P30CA016672 to The University of Texas M. D. Anderson Cancer Center. The authors declare no conflicts of interest. Publisher Copyright: © 2019 The Author(s).

PY - 2019

Y1 - 2019

N2 - AMPKis a crucial regulator of energyhomeostasis that acts downstream of its upstream kinase liver kinaseB1 (LKB1) and calcium/calmodulin-dependent protein kinase 2 (CaMKK2). LKB1 primarily phosphorylates AMPK after energy stress,whereas calcium-mediated activation ofAMPKrequiresCaMKK2, although the regulatorymechanisms of calcium-mediated AMPK activation remain unclear. Using biochemical, microscopic, and genetic approaches, we demonstrate that the stromal interaction molecule (STIM)2, a calcium sensor, acts as a novel regulator of CaMKK2-AMPK signaling.Wereveal that STIM2 interacts withAMPKand CaMKK2 and that the increase in intracellular calcium levels promotesAMPKcolocalization and interactionwith STIM2.We further show that STIM2 deficiency attenuates calciuminduced but not energy stress-induced AMPK activation, possibly by regulating the CaMKK2-AMPK interaction. Together, our results identify a previously unappreciated mechanism that modulates calcium-mediated AMPK activation.

AB - AMPKis a crucial regulator of energyhomeostasis that acts downstream of its upstream kinase liver kinaseB1 (LKB1) and calcium/calmodulin-dependent protein kinase 2 (CaMKK2). LKB1 primarily phosphorylates AMPK after energy stress,whereas calcium-mediated activation ofAMPKrequiresCaMKK2, although the regulatorymechanisms of calcium-mediated AMPK activation remain unclear. Using biochemical, microscopic, and genetic approaches, we demonstrate that the stromal interaction molecule (STIM)2, a calcium sensor, acts as a novel regulator of CaMKK2-AMPK signaling.Wereveal that STIM2 interacts withAMPKand CaMKK2 and that the increase in intracellular calcium levels promotesAMPKcolocalization and interactionwith STIM2.We further show that STIM2 deficiency attenuates calciuminduced but not energy stress-induced AMPK activation, possibly by regulating the CaMKK2-AMPK interaction. Together, our results identify a previously unappreciated mechanism that modulates calcium-mediated AMPK activation.

KW - CaMKK2

KW - Energy stress

KW - LKB1

KW - STIM1

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JF - FASEB Journal

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ER -

STIM2 interacts with AMPK and regulates calcium-induced AMPK activation

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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