Protein-coding gene in the species Homo sapiens
NUAK family SNF1-like kinase 1 also known as AMPK-related protein kinase 5 (ARK5) is anenzyme that in humans is encoded by theNUAK1 gene .[ 5] [ 6] [ 7]
Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex.[ 8]
Clinical significance [ edit ] ARK5 is important in tumor malignancy and invasiveness.[ 9]
ARK5 is often overexpressed inmultiple myeloma cell lines.[ 10] [ 11] Akt .[ 9]
ARK5 increasesMT1-MMP production.[ 9] MMP-2 andMMP-9 which are involved in tumormetastasis .[ 9]
ON123300 (aCDK4 inhibitor), also inhibits ARK5 and reduces proliferation ofmultiple myeloma andmantle cell lymphoma cell lines.[ 10]
NUAK1 has been shown tointeract withUSP9X [ 12] Ubiquitin C .[ 12]
^a b c GRCh38: Ensembl release 89: ENSG00000074590 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000020032 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Lavin MF, Esumi H (Dec 2002)."Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein" (PDF) .J Biol Chem .278 (1):48– 53.doi :10.1074/jbc.M206025200 PMID 12409306 .S2CID 23605132 . ^ Suzuki A, Kusakai G, Kishimoto A, Lu J, Ogura T, Esumi H (Sep 2003). "ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation".Oncogene .22 (40):6177– 82.doi :10.1038/sj.onc.1206899 .PMID 13679856 .S2CID 20975883 . ^ "Entrez Gene: NUAK1 NUAK family, SNF1-like kinase, 1" .^ Protein Coding (2021-11-14)."NUAK1 Gene - NUAK Family Kinase 1" .Gene Cards . Retrieved2021-12-19 . ^a b c d Suzuki A, Lu J, Kusakai G, et al. (2004)."ARK5 is a tumor invasion-associated factor downstream of Akt signaling" .Mol. Cell. Biol .24 (8):3526– 35.doi :10.1128/MCB.24.8.3526-3535.2004 .PMC 381626 PMID 15060171 . ^a b Multi-Target Drug Blocks Myeloma Proliferation. March 2016 ^ Deepak Perumal, et al. (2014). "Abstract 1324: Dual targeting of CDK4 and ARK5 using a novel kinase inhibitor ON123300 is effective in vitro and in vivo in Multiple Myeloma".Cancer Research .74 (19_Supplement): 1324.doi :10.1158/1538-7445.AM2014-1324 . ^a b Al-Hakim AK, Zagorska Anna, Chapman Louise, Deak Maria, Peggie Mark, Alessi Dario R (Apr 2008)."Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains" (PDF) .Biochem. J .411 (2). England:249– 60.doi :10.1042/BJ20080067 .PMID 18254724 .S2CID 13038944 . Nagase T, Ishikawa K, Miyajima N, et al. (1998)."Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro" .DNA Res .5 (1):31– 9.doi :10.1093/dnares/5.1.31 PMID 9628581 . Ota T, Suzuki Y, Nishikawa T, et al. (2004)."Complete sequencing and characterization of 21,243 full-length human cDNAs" .Nat. Genet .36 (1):40– 5.doi :10.1038/ng1285 PMID 14702039 . Lizcano JM, Göransson O, Toth R, et al. (2005)."LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1" .EMBO J .23 (4):833– 43.doi :10.1038/sj.emboj.7600110 .PMC 381014 PMID 14976552 . Suzuki A, Kusakai G, Kishimoto A, et al. (2004). "Regulation of caspase-6 and FLIP by the AMPK family member ARK5".Oncogene .23 (42):7067– 75.doi :10.1038/sj.onc.1207963 .PMID 15273717 .S2CID 13635036 . Kusakai G, Suzuki A, Ogura T, et al. (2005). "Strong association of ARK5 with tumor invasion and metastasis".J. Exp. Clin. Cancer Res .23 (2):263– 8.PMID 15354411 . Suzuki A, Iida S, Kato-Uranishi M, et al. (2006)."ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma" .Oncogene .24 (46):6936– 44.doi :10.1038/sj.onc.1208844 PMID 16044163 . Al-Hakim AK, Göransson O, Deak M, et al. (2006). "14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK".J. Cell Sci .118 (Pt 23):5661– 73.doi :10.1242/jcs.02670 .PMID 16306228 .S2CID 17404931 . Suzuki A, Ogura T, Esumi H (2006)."NDR2 acts as the upstream kinase of ARK5 during insulin-like growth factor-1 signaling" .J. Biol. Chem .281 (20):13915– 21.doi :10.1074/jbc.M511354200 PMID 16488889 . Ewing RM, Chu P, Elisma F, et al. (2007)."Large-scale mapping of human protein-protein interactions by mass spectrometry" .Mol. Syst. Biol .3 (1): 89.doi :10.1038/msb4100134 .PMC 1847948 PMID 17353931 .
Activity Regulation Classification Kinetics Types
