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Gene Review

MARCKS  -  myristoylated alanine-rich protein kinase...

Homo sapiens

Synonyms: 80K-L, 80K-L protein, MACS, Myristoylated alanine-rich C-kinase substrate, PKCSL, ...
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Disease relevance of MARCKS


Psychiatry related information on MARCKS


High impact information on MARCKS


Chemical compound and disease context of MARCKS


Biological context of MARCKS

  • Melanocytes incubated for 48 h with TPA at a higher concentration (100 ng/ml TPA) exhibited suboptimal TPA-stimulated DNA synthesis (28% of maximal) and decreased phosphorylation of the MARCKS substrate protein (50% of maximal) [16].
  • Down-regulation of MARCKS expression or disruption of MARCKS function in these cells inhibits the secretory response to subsequent stimulation [17].
  • In parallel with the sustained increase in diglyceride formation, CR-mediated phagocytosis was also associated with phosphorylation of a cellular protein kinase C substrate (MARCKS) [18].
  • Dephosphorylated cytoplasmic MARCKS would also be free to interact with mucin granule membranes and thus could link granules to the contractile cytoskeleton, mediating their movement to the cell periphery and subsequent exocytosis [17].
  • Plasmid constructions containing between 52 and 1453 bp of the human MARCKS promoter linked to the human growth hormone gene were then used in transient expression experiments [19].

Anatomical context of MARCKS

  • MARCKS, a major in vivo substrate of protein kinase C, interacts with plasma membranes in a phosphorylation-, myristoylation-, and calmodulin-dependent manner [20].
  • The human cDNA was used to demonstrate that tumor necrosis factor-alpha could rapidly stimulate MARCKS gene transcription in the human promyelocytic leukemia cell line HL60 [19].
  • Endogenous MARCKS and green fluorescent protein-tagged wild-type MARCKS were translocated from membrane to cytosol upon PMA treatment, further confirming MARCKS activation [21].
  • MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro [17].
  • These data provide evidence for the identity of the MCE as cathepsin B and suggest that this cleavage most likely takes place within lysosomes, perhaps as a result of specific lysosomal targeting sequences within the MARCKS primary sequence [22].

Associations of MARCKS with chemical compounds

  • Myristoylated alanine-rich C kinase substrate (MARCKS) sequesters spin-labeled phosphatidylinositol 4,5-bisphosphate in lipid bilayers [23].
  • We previously identified a novel means of regulating cellular MARCKS concentrations that involved a specific proteolytic cleavage of the protein and implicated a cysteine protease in this process (Spizz, G., and Blackshear, P. J. (1996) J. Biol. Chem. 271, 553-562) [22].
  • A quantitative analysis obtained with dansyl (5-dimethylaminonaphthalene-1-sulfonyl)-calmodulin showed that myristoylated MARCKS has an affinity higher than the non-myristoylated protein [20].
  • The phosphorylation of PKC-delta was inhibited by C3 toxin, demonstrating that the role of MARCKS in NT secretion was regulated by PKC-delta downstream of the Rho/ROK pathway [21].
  • The ability of TPA to enhance NA release and to cause the translocation and phosphorylation of MARCKS was inhibited by the PKC inhibitor Ro 31-8220 (10 microM) [13].

Enzymatic interactions of MARCKS


Regulatory relationships of MARCKS


Other interactions of MARCKS

  • Identification and characterization of cathepsin B as the cellular MARCKS cleaving enzyme [22].
  • BBS-mediated NT secretion was attenuated by MARCKS siRNA [21].
  • Our results show that MARCKS is an essential link in the PKC-mediated activation of PtdCho-specific PLD in these cells and that the stimulation of PtdCho synthesis by PMA is a secondary response [2].
  • Sprouting neuritic components of plaques are immunopositive with other growth-associated proteins, such as GAP43, MARCKS, and spectrin [28].
  • Analogous structural motifs in myelin basic protein and in MARCKS [29].

Analytical, diagnostic and therapeutic context of MARCKS


  1. Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability. Kim, N.G., Rhee, H., Li, L.S., Kim, H., Lee, J.S., Kim, J.H., Kim, N.K., Kim, H. Oncogene (2002) [Pubmed]
  2. Overexpression of myristoylated alanine-rich C-kinase substrate enhances activation of phospholipase D by protein kinase C in SK-N-MC human neuroblastoma cells. Morash, S.C., Rosé, S.D., Byers, D.M., Ridgway, N.D., Cook, H.W. Biochem. J. (1998) [Pubmed]
  3. Protein kinase C isoforms and growth, differentiation and phosphatidylcholine turnover in human neuroblastoma cells. Cook, H.W., Morash, S.C., Rosé, S.D., Ridgway, N.D., Byers, D.M. Journal of lipid mediators and cell signalling. (1996) [Pubmed]
  4. Overexpression of the myristoylated alanine-rich C kinase substrate in human choroidal melanoma cells affects cell proliferation. Manenti, S., Malecaze, F., Chap, H., Darbon, J.M. Cancer Res. (1998) [Pubmed]
  5. Insulin activation of protein kinase C: a reassessment. Blackshear, P.J., Haupt, D.M., Stumpo, D.J. J. Biol. Chem. (1991) [Pubmed]
  6. Expression of the myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) in the prefrontal cortex and hippocampus of suicide victims. McNamara, R.K., Hyde, T.M., Kleinman, J.E., Lenox, R.H. The Journal of clinical psychiatry. (1999) [Pubmed]
  7. Myristoylated alanine-rich C kinase substrate (MARCKS): a molecular target for the therapeutic action of mood stabilizers in the brain? Lenox, R.H., McNamara, R.K., Watterson, J.M., Watson, D.G. The Journal of clinical psychiatry. (1996) [Pubmed]
  8. Protein kinase C regulates the nuclear localization of diacylglycerol kinase-zeta. Topham, M.K., Bunting, M., Zimmerman, G.A., McIntyre, T.M., Blackshear, P.J., Prescott, S.M. Nature (1998) [Pubmed]
  9. Continuous membrane-cytoskeleton adhesion requires continuous accommodation to lipid and cytoskeleton dynamics. Sheetz, M.P., Sable, J.E., Döbereiner, H.G. Annual review of biophysics and biomolecular structure. (2006) [Pubmed]
  10. PIP(2) and proteins: interactions, organization, and information flow. McLaughlin, S., Wang, J., Gambhir, A., Murray, D. Annual review of biophysics and biomolecular structure. (2002) [Pubmed]
  11. A role for MARCKS, the alpha isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages. Allen, L.H., Aderem, A. J. Exp. Med. (1995) [Pubmed]
  12. Overexpression of MARCKS, but not protein kinase C-alpha, increases phorbol ester-stimulated synthesis of phosphatidylcholine in human SK-N-MC neuroblastoma cells. Rose, S.D., Morash, S.C., Ridgway, D.N., Byers, D.M., Cook, H.W. J. Neurochem. (1996) [Pubmed]
  13. Activation of protein kinase C-alpha and translocation of the myristoylated alanine-rich C-kinase substrate correlate with phorbol ester-enhanced noradrenaline release from SH-SY5Y human neuroblastoma cells. Goodall, A.R., Turner, N.A., Walker, J.H., Ball, S.G., Vaughan, P.F. J. Neurochem. (1997) [Pubmed]
  14. Comparison study of the expressions of myristoylated alanine-rich C kinase substrate in hepatocellular carcinoma, liver cirrhosis, chronic hepatitis, and normal liver. Masaki, T., Tokuda, M., Yoshida, S., Nakai, S., Morishita, A., Uchida, N., Funaki, T., Kita, Y., Funakoshi, F., Nonomura, T., Himoto, T., Deguchi, A., Kimura, Y., Izuishi, K., Wakabayashi, H., Usuki, H., Yoshiji, H., Watanabe, S., Kurokohchi, K., Kuriyama, S. Int. J. Oncol. (2005) [Pubmed]
  15. Rho-associated kinase phosphorylates MARCKS in human neuronal cells. Nagumo, H., Ikenoya, M., Sakurada, K., Furuya, K., Ikuhara, T., Hiraoka, H., Sasaki, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  16. Growth of human melanocyte cultures supported by 12-O-tetradecanoylphorbol-13-acetate is mediated through protein kinase C activation. Arita, Y., O'Driscoll, K.R., Weinstein, I.B. Cancer Res. (1992) [Pubmed]
  17. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. Li, Y., Martin, L.D., Spizz, G., Adler, K.B. J. Biol. Chem. (2001) [Pubmed]
  18. Complement receptor-mediated phagocytosis is associated with accumulation of phosphatidylcholine-derived diglyceride in human neutrophils. Involvement of phospholipase D and direct evidence for a positive feedback signal of protein kinase. Fällman, M., Gullberg, M., Hellberg, C., Andersson, T. J. Biol. Chem. (1992) [Pubmed]
  19. The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization. Harlan, D.M., Graff, J.M., Stumpo, D.J., Eddy, R.L., Shows, T.B., Boyle, J.M., Blackshear, P.J. J. Biol. Chem. (1991) [Pubmed]
  20. Direct involvement of protein myristoylation in myristoylated alanine-rich C kinase substrate (MARCKS)-calmodulin interaction. Matsubara, M., Titani, K., Taniguchi, H., Hayashi, N. J. Biol. Chem. (2003) [Pubmed]
  21. Myristoylated alanine-rich C kinase substrate-mediated neurotensin release via protein kinase C-delta downstream of the Rho/ROK pathway. Li, J., O'Connor, K.L., Greeley, G.H., Blackshear, P.J., Townsend, C.M., Evers, B.M. J. Biol. Chem. (2005) [Pubmed]
  22. Identification and characterization of cathepsin B as the cellular MARCKS cleaving enzyme. Spizz, G., Blackshear, P.J. J. Biol. Chem. (1997) [Pubmed]
  23. Myristoylated alanine-rich C kinase substrate (MARCKS) sequesters spin-labeled phosphatidylinositol 4,5-bisphosphate in lipid bilayers. Rauch, M.E., Ferguson, C.G., Prestwich, G.D., Cafiso, D.S. J. Biol. Chem. (2002) [Pubmed]
  24. New aspects of neurotransmitter release and exocytosis: Rho-kinase-dependent myristoylated alanine-rich C-kinase substrate phosphorylation and regulation of neurofilament structure in neuronal cells. Sasaki, Y. J. Pharmacol. Sci. (2003) [Pubmed]
  25. Differential induction of phosphatidylcholine hydrolysis, diacylglycerol formation and protein kinase C activation by epidermal growth factor and transforming growth factor-alpha in normal human skin fibroblasts and keratinocytes. Reynolds, N.J., Talwar, H.S., Baldassare, J.J., Henderson, P.A., Elder, J.T., Voorhees, J.J., Fisher, G.J. Biochem. J. (1993) [Pubmed]
  26. Role of MARCKS in regulating endothelial cell proliferation. Zhao, Y., Neltner, B.S., Davis, H.W. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  27. Nanomolar amyloid beta protein activates a specific PKC isoform mediating phosphorylation of MARCKS in Neuro2A cells. Tanimukai, S., Hasegawa, H., Nakai, M., Yagi, K., Hirai, M., Saito, N., Taniguchi, T., Terashima, A., Yasuda, M., Kawamata, T., Tanaka, C. Neuroreport (2002) [Pubmed]
  28. Hyperactivation of signal transduction systems in Alzheimer's disease. Saitoh, T., Horsburgh, K., Masliah, E. Ann. N. Y. Acad. Sci. (1993) [Pubmed]
  29. Analogous structural motifs in myelin basic protein and in MARCKS. Harauz, G., Ishiyama, N., Bates, I.R. Mol. Cell. Biochem. (2000) [Pubmed]
  30. Myristoylation-dependent and electrostatic interactions exert independent effects on the membrane association of the myristoylated alanine-rich protein kinase C substrate protein in intact cells. Swierczynski, S.L., Blackshear, P.J. J. Biol. Chem. (1996) [Pubmed]
  31. Phospholipase D activity is altered in X-linked adrenoleukodystrophy heterozygous carriers, but not in hemizygous patients. Logan, H.E., Byers, D.M., Ridgway, N.D., Cook, H.W. Biochim. Biophys. Acta (1998) [Pubmed]
  32. Isolation of proximal and distal tubule cells from human kidney by immunomagnetic separation. Technical note. Baer, P.C., Nockher, W.A., Haase, W., Scherberich, J.E. Kidney Int. (1997) [Pubmed]
  33. Molecular cloning and chromosomal mapping of a cDNA encoding human 80K-L protein: major substrate for protein kinase C. Sakai, K., Hirai, M., Kudoh, J., Minoshima, S., Shimizu, N. Genomics (1992) [Pubmed]
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