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Gene Review

MARK2  -  MAP/microtubule affinity-regulating kinase 2

Homo sapiens

Synonyms: ELKL motif kinase 1, EMK-1, EMK1, PAR-1, PAR-1B, ...
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Disease relevance of MARK2

  • In conclusion, flot-2 overexpression is associated with melanoma progression, with increased PAR-1 expression, and with transformation of SB2 melanoma cells to a highly metastatic line [1].
  • Flot-2 binds to PAR-1, a known upstream mediator of major signal transduction pathways implicated in cell growth and metastasis, and may thereby influence tumor progression [1].
  • These results support a role for proteinases and PARs in intestinal disease and provide new directions for possible therapeutic applications of PAR1 antagonists [2].
  • OBJECTIVE: The purpose is to examine the responsiveness of the Health Utilities Index Mark 2 (HUI2), Mark 3 (HUI3), and other generic and disease-specific measures in osteoarthritis patients undergoing total hip arthroplasty (THA) [3].
  • However, except in invasive lobular carcinoma (ILC) and inflammatory breast carcinoma (IBC), CE-CT showed the best correlation (R insertion mark2 = 0.537) [4].

Psychiatry related information on MARK2

  • We suggest that although the four MARK/PAR-1 kinases might play multiple cellular roles in concert with different targets, MARK4 is likely to be directly involved in microtubule organization in neuronal cells and may contribute to the pathological phosphorylation of tau in Alzheimer's disease [5].
  • Psychometric properties of the Health Utilities Index Mark 2 system in paediatric oncology patients [6].

High impact information on MARK2

  • Treating cells with Wnt increases endogenous PAR-1 activity coincident with Dsh phosphorylation [7].
  • The PAR-1 project resulted in a pharmacological tool compound that facilitated in vivo proof-of-principle studies, whereas the vasopressin and fibrinogen receptor projects resulted in several preclinical development compounds, three of which advanced into human clinical trials [8].
  • Conversely, EMK1 overexpression induced the appearance of intercellular lumina and horizontal MT arrays in MDCK cells, making EMK1 the first known candidate to regulate the developmental branching decision between hepatic and columnar epithelial cells [9].
  • Knocking down MARK2 expression with small interfering RNAs induced formation of multiple axon-like neurites and promoted axon outgrowth [10].
  • Ectopic expression of MARK2 caused phosphorylation of tau (S262) and led to loss of axons, and this phenotype was rescued by expression of PAR-3, PAR-6, and aPKC [10].

Biological context of MARK2


Anatomical context of MARK2


Associations of MARK2 with chemical compounds

  • These results indicate that phosphorylation of Rab11-FIP2 on serine 227 by MARK2 regulates an alternative pathway modulating the establishment of epithelial polarity [20].
  • The formation of neurites in N2a cells is blocked if MARK2 is inactivated, either by transfecting a dominant negative mutant, or by MARK2 inhibitors such as hymenialdisine [21].
  • Higher platelet reactivity associated with PAR-1 IVSn-14 A allele homozygotes persists despite clopidogrel therapy [22].
  • Vapour concentrations from a halothane Cyprane (Fluotec) Mark 2 increased in relation to the density of carrier gas, whereas the concentrations delivered by an enflurane Ohio vaporizer decreased [23].
  • Background: The role of the tyrosine kinase pp60(src) in PAR-1-dependent Ca(2+) entry was investigated in human platelets. pp60(src) plays a role in thapsigargin (TG)-evoked store-operated Ca(2+) entry (SOCE), which is thought to be a major component of thrombin-evoked Ca(2+) entry [24].

Regulatory relationships of MARK2

  • PAK5 suppresses the activity of MARK2 toward its target, tau protein [18].

Other interactions of MARK2

  • The adult statures of a sample of 71 Canadian boys from the Saskatchewan Longitudinal Growth Study were predicted using the original TW Mark 1 and the new TW Mark 2 prediction equations [25].
  • We report the X-ray structure of the catalytic and ubiquitin-associated domains (UBA) of human MARK2 [15].
  • Human EMK1 is located on 11q12-q13, close to COX8 and FTH1 [26].
  • The results point to an inverse relationship between actin- and microtubule-related signaling by the PAK5 and MARK2 pathways that affect both cytoskeletal networks [18].
  • We identify EMK and C-TAK1, two members of the microtubule affinity-regulating kinase (MARK)/Par-1 family, as regulators of this process [27].

Analytical, diagnostic and therapeutic context of MARK2

  • By Northern blot, human EMK1 was shown to be encoded by a single mRNA ubiquitously expressed [14].
  • Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients [17].
  • We examine the relationship between Visual Analogue Scale (VAS) and Standard Gamble (SG) assumed in the development of the multiplicative multi-attribute utility functions (M-MAUFs) for the Health Utilities Index (HUI) Mark 2 and Mark 3, using data from a UK valuation study of the HUI2 [28].
  • A decrease of 0.1 units in HUI Mark 2 (HUI2) self-care single-attribute utility score was associated with an increased hazard of death of 30% (P = .023) for patients with low-grade tumors (n=25) [29].
  • A portable Mark 2 aid was developed to enable clinical trials to be carried out on profoundly deaf people [30].


  1. Up-regulation of Flotillin-2 is associated with melanoma progression and modulates expression of the thrombin receptor protease activated receptor 1. Hazarika, P., McCarty, M.F., Prieto, V.G., George, S., Babu, D., Koul, D., Bar-Eli, M., Duvic, M. Cancer Res. (2004) [Pubmed]
  2. Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability. Chin, A.C., Vergnolle, N., MacNaughton, W.K., Wallace, J.L., Hollenberg, M.D., Buret, A.G. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. Is the Health Utilities Index responsive in total hip arthroplasty patients? Blanchard, C., Feeny, D., Mahon, J.L., Bourne, R., Rorabeck, C., Stitt, L., Webster-Bogaert, S. Journal of clinical epidemiology. (2003) [Pubmed]
  4. Accuracy of contrast-enhanced computed tomography in the prediction of residual breast cancer after neoadjuvant chemotherapy. Akashi-Tanaka, S., Fukutomi, T., Watanabe, T., Katsumata, N., Nanasawa, T., Matsuo, K., Miyakawa, K., Tsuda, H. Int. J. Cancer (2001) [Pubmed]
  5. MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes. Trinczek, B., Brajenovic, M., Ebneth, A., Drewes, G. J. Biol. Chem. (2004) [Pubmed]
  6. Psychometric properties of the Health Utilities Index Mark 2 system in paediatric oncology patients. Trudel, J.G., Rivard, M., Dobkin, P.L., Leclerc, J.M., Robaey, P. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. (1998) [Pubmed]
  7. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Sun, T.Q., Lu, B., Feng, J.J., Reinhard, C., Jan, Y.N., Fantl, W.J., Williams, L.T. Nat. Cell Biol. (2001) [Pubmed]
  8. Adventures in drug discovery: potent agents based on ligands for cell-surface receptors. Maryanoff, B.E. Acc. Chem. Res. (2006) [Pubmed]
  9. Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton. Cohen, D., Brennwald, P.J., Rodriguez-Boulan, E., Müsch, A. J. Cell Biol. (2004) [Pubmed]
  10. Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity. Chen, Y.M., Wang, Q.J., Hu, H.S., Yu, P.C., Zhu, J., Drewes, G., Piwnica-Worms, H., Luo, Z.G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. GSK-3beta directly phosphorylates and activates MARK2/PAR-1. Kosuga, S., Tashiro, E., Kajioka, T., Ueki, M., Shimizu, Y., Imoto, M. J. Biol. Chem. (2005) [Pubmed]
  12. The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation. Jaleel, M., Villa, F., Deak, M., Toth, R., Prescott, A.R., Van Aalten, D.M., Alessi, D.R. Biochem. J. (2006) [Pubmed]
  13. The C. elegans MELK ortholog PIG-1 regulates cell size asymmetry and daughter cell fate in asymmetric neuroblast divisions. Cordes, S., Frank, C.A., Garriga, G. Development (2006) [Pubmed]
  14. Human serine/threonine protein kinase EMK1: genomic structure and cDNA cloning of isoforms produced by alternative splicing. Espinosa, L., Navarro, E. Cytogenet. Cell Genet. (1998) [Pubmed]
  15. Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1. Panneerselvam, S., Marx, A., Mandelkow, E.M., Mandelkow, E. Structure (2006) [Pubmed]
  16. aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Suzuki, A., Hirata, M., Kamimura, K., Maniwa, R., Yamanaka, T., Mizuno, K., Kishikawa, M., Hirose, H., Amano, Y., Izumi, N., Miwa, Y., Ohno, S. Curr. Biol. (2004) [Pubmed]
  17. Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients. Hueso, M., Beltran, V., Moreso, F., Ciriero, E., Fulladosa, X., Grinyó, J.M., Serón, D., Navarro, E. Biochim. Biophys. Acta (2004) [Pubmed]
  18. PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable microtubules and dynamic actin. Matenia, D., Griesshaber, B., Li, X.Y., Thiessen, A., Johne, C., Jiao, J., Mandelkow, E., Mandelkow, E.M. Mol. Biol. Cell (2005) [Pubmed]
  19. Par-1 promotes a hepatic mode of apical protein trafficking in MDCK cells. Cohen, D., Rodriguez-Boulan, E., Müsch, A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells. Ducharme, N.A., Hales, C.M., Lapierre, L.A., Ham, A.J., Oztan, A., Apodaca, G., Goldenring, J.R. Mol. Biol. Cell (2006) [Pubmed]
  21. Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. Biernat, J., Wu, Y.Z., Timm, T., Zheng-Fischhöfer, Q., Mandelkow, E., Meijer, L., Mandelkow, E.M. Mol. Biol. Cell (2002) [Pubmed]
  22. PAR-1 genotype influences platelet aggregation and procoagulant responses in patients with coronary artery disease prior to and during clopidogrel therapy. Smith, S.M., Judge, H.M., Peters, G., Armstrong, M., Dupont, A., Gaussem, P., Storey, R.F. Platelets (2005) [Pubmed]
  23. An evaluation of gas density dependence of anaesthetic vaporizers. Prins, L., Strupat, J., Clement, J., Knill, R.L. Canadian Anaesthetists' Society journal. (1980) [Pubmed]
  24. PAR-1-dependent pp60(src) activation is dependent on protein kinase C and increased [Ca(2+)]: evidence that pp60(src) does not regulate PAR-1-dependent Ca(2+) entry in human platelets. Harper, M.T., Sage, S.O. J. Thromb. Haemost. (2006) [Pubmed]
  25. The application of new height-prediction equations (Tanner-Whitehouse mark 2) to a sample of Canadian boys. Cameron, N., Mirwald, R.L., Bailey, D.A., Davies, P.S. Ann. Hum. Biol. (1985) [Pubmed]
  26. Human EMK1 is located on 11q12-q13, close to COX8 and FTH1. Courseaux, A., Fernandes, M., Grosgeorge, J., Inglis, J., Raynaud, S.D., Gaudray, P. Mamm. Genome (1995) [Pubmed]
  27. New Role for hPar-1 Kinases EMK and C-TAK1 in Regulating Localization and Activity of Class IIa Histone Deacetylases. Dequiedt, F., Martin, M., Von Blume, J., Vertommen, D., Lecomte, E., Mari, N., Heinen, M.F., Bachmann, M., Twizere, J.C., Huang, M.C., Rider, M.H., Piwnica-Worms, H., Seufferlein, T., Kettmann, R. Mol. Cell. Biol. (2006) [Pubmed]
  28. Mapping between Visual Analogue Scale and Standard Gamble data; results from the UK Health Utilities Index 2 valuation survey. Stevens, K.J., McCabe, C.J., Brazier, J.E. Health economics. (2006) [Pubmed]
  29. Health status measurements at diagnosis as predictors of survival among adults with brain tumors. McCarter, H., Furlong, W., Whitton, A.C., Feeny, D., DePauw, S., Willan, A.R., Barr, R.D. J. Clin. Oncol. (2006) [Pubmed]
  30. Electrical stimulation at the wrist as an aid for the profoundly deaf. Dodgson, G.S., Brown, B.H., Freeston, I.L., Stevens, J.C. Clinical physics and physiological measurement : an official journal of the Hospital Physicists' Association, Deutsche Gesellschaft für Medizinische Physik and the European Federation of Organisations for Medical Physics. (1983) [Pubmed]
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