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STK11

MIM.602216 19p13.3

XEEK1, LKB1

 

STK11 is a serine-threonine protein kinase mutated in patients with an autosomal dominantly inherited cancer syndrome predisposing to multiple benign and malignant tumours, termed Peutz-Jeghers syndrome.

LKB1 has been implicated as a regulator of multiple biological processes and signaling pathways, including the control of cell-cycle arrest, p53-mediated apoptosis, Wnt signaling, transforming growth factor (TGF)-beta signaling, ras-induced cell transformation, and energy metabolism.

Function

-  nullizygosity provokes a poorly understood constellation of developmental perturbations in the mid-gestational mouse
-  specific inhibition of XEEK1, the Xenopus orthologue of STK11 , engendered developmental anomalies - shortened body axis and defective dorsoanterior patterning - associated previously with aberrant Wnt signalling.
-  STK11 cooperates with the Wnt-beta-catenin signalling in axis induction and modulates the expression of Wnt-responsive genes in both Xenopus embryos and mammalian cells.
-  STK11 /XEEK1 acts upstream of beta-catenin in the Wnt-beta-catenin pathway in vivo.
-  STK11 /XEEK1 regulates glycogen synthase kinase (GSK)3beta phosphorylation and it is physically associated in vivo with GSK3beta and protein kinase C (PKC)-zeta, a known GSK3 kinase.
-  STK11 /XEEK1 is required for Wnt-beta-catenin signalling in frogs and mammals
-  STK11 functions as a tumour suppressor perhaps by controlling cell polarity

Pathology

-  germline mutations of the STK11 gene lead to Peutz-Jeghers syndrome

Animal models

-  Lkb1(-/-) knock-out mice (#12060709#)

References

-  Hardie DG. New roles for the LKB1-->AMPK pathway. Curr Opin Cell Biol. 2005 Apr;17(2):167-73. PMID: #15780593#

-  Spicer J, Ashworth A. LKB1 kinase: master and commander of metabolism and polarity. Curr Biol. 2004 May 25;14(10):R383-5. PMID: #15186763#

-  Baas AF, Smit L, Clevers H. LKB1 tumor suppressor protein: PARtaker in cell polarity. Trends Cell Biol. 2004 Jun;14(6):312-9. PMID: #15183188#

-  Yoo LI, Chung DC, Yuan J. LKB1, a master tumour suppressor of the small intestine and beyond. Nat Rev Cancer. 2002 Jul;2(7):529-35. PMID: #12094239#

-  Boudeau J, Sapkota G, Alessi DR. LKB1, a protein kinase regulating cell proliferation and polarity. FEBS Lett. 2003 Jul 3;546(1):159-65. PMID: #12829253#



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