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LKB1 is a master ki...
LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
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Lizcano, Jose M (författare)
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- Göransson, Olga (författare)
- Lund University,Lunds universitet,Signaltransduktionsforskning,Forskargrupper vid Lunds universitet,Insulin Signal Transduction,Lund University Research Groups
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Toth, Rachel (författare)
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Deak, Maria (författare)
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Morrice, Nick A (författare)
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Boudeau, Jerome (författare)
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Hawley, Simon A (författare)
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Udd, Lina (författare)
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Makela, Tomi P (författare)
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Hardie, D Grahame (författare)
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Alessi, Dario R (författare)
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visa färre...
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(creator_code:org_t)
- 2004-02-19
- 2004
- Engelska.
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Ingår i: EMBO Journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 23:4, s. 833-843
- Relaterad länk:
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- We recently demonstrated that the LKB1 tumour suppressor kinase, in complex with the pseudokinase STRAD and the scaffolding protein MO25, phosphorylates and activates AMP-activated protein kinase (AMPK). A total of 12 human kinases (NUAK1, NUAK2, BRSK1, BRSK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4 and MELK) are related to AMPK. Here we demonstrate that LKB1 can phosphorylate the T-loop of all the members of this subfamily, apart from MELK, increasing their activity >50-fold. LKB1 catalytic activity and the presence of MO25 and STRAD are required for activation. Mutation of the T-loop Thr phosphorylated by LKB1 to Ala prevented activation, while mutation to glutamate produced active forms of many of the AMPK-related kinases. Activities of endogenous NUAK2, QIK, QSK, SIK, MARK1, MARK2/3 and MARK4 were markedly reduced in LKB1-deficient cells. Neither LKB1 activity nor that of AMPK-related kinases was stimulated by phenformin or AICAR, which activate AMPK. Our results show that LKB1 functions as a master upstream protein kinase, regulating AMPK-related kinases as well as AMPK. Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- diabetes
- PAR1/MARK kinase
- cancer
- cell polarity
- TOF–TOF mass spectrometry
- Peutz–Jeghers syndrome
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Lizcano, Jose M
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Göransson, Olga
-
Toth, Rachel
-
Deak, Maria
-
Morrice, Nick A
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Boudeau, Jerome
-
visa fler...
-
Hawley, Simon A
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Udd, Lina
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Makela, Tomi P
-
Hardie, D Graham ...
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Alessi, Dario R
-
visa färre...
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EMBO Journal
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Lunds universitet