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Gene Review

MAPKAP1  -  mitogen-activated protein kinase...

Homo sapiens

Synonyms: JC310, MGC2745, MIP1, Mitogen-activated protein kinase 2-associated protein 1, SAPK-interacting protein 1, ...
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Disease relevance of MAPKAP1


Psychiatry related information on MAPKAP1


High impact information on MAPKAP1

  • SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity [7].
  • The MAPKs coordinately regulate cell proliferation, differentiation, motility, and survival, which are functions also known to be mediated by members of a growing family of MAPK-activated protein kinases (MKs; formerly known as MAPKAP kinases) [8].
  • The stimulatory effect of SIN-1 was maximal at 1 nM (approximately 2-fold increase in ICa) and was comparable with the effect of a saturating concentration (1 microM) of isoprenaline, a beta-adrenergic agonist [9].
  • To examine whether NO also regulates Ca2+ channels in human heart, we investigated the effects of SIN-1 on ICa in isolated human atrial myocytes [9].
  • Because, in frog heart, the stimulatory effect of SIN-1 on ICa was found to be due to cGMP-induced inhibition of cGMP-inhibited phosphodiesterase (cGI-PDE), we compared the effects of SIN-1 and milrinone, a cGI-PDE selective inhibitor, on ICa in human [9].

Chemical compound and disease context of MAPKAP1


Biological context of MAPKAP1

  • The orthologous proteins of the stress-activated protein kinase-interacting 1 (Sin1) family have been implicated in several different signal transduction pathways [14].
  • Alternative polyadenylation and splicing of mRNAs transcribed from the human Sin1 gene [15].
  • In this study, we have investigated the function of the full-length human Sin1 protein and a C-terminally truncated isoform, Sin1alpha, which is produced by alternative splicing [14].
  • Genetic ablation of sin1 abolished Akt-Ser473 phosphorylation and disrupted rictor-mTOR interaction but maintained Thr308 phosphorylation [7].
  • Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation [16].

Anatomical context of MAPKAP1


Associations of MAPKAP1 with chemical compounds

  • Recently, we found that the NO-donor SIN-1 (3-morpholino-sydnonimine) exerts a dual regulation of ICa in frog ventricular myocytes via an accumulation of cGMP [9].
  • Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the .NO and O2.- generator SIN-1 (3-morpholinosydnonimine) was inhibited more effectively by gammaT than alphaT [22].
  • The effects of SIN-1 on platelet function were associated with a significant increase in platelet cyclic GMP concentration from baseline (3.15 +/- 0.88 versus 1.58 +/- 0.73 pmol/10(9) platelets, p < 0.005) [1].
  • In addition, the antibiotic also inhibited the cGMP increases triggered by SNP, S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosyndomidine (SIN-1) but failed to prevent an increase in cGMP caused by nitrosylated albumin [23].
  • LPS did not alter the hypotensive responses induced by phentolamine, verapamil, or SIN-1 [24].

Physical interactions of MAPKAP1


Regulatory relationships of MAPKAP1

  • Over-expression of full-length Sin1 inhibited the activation of JNK by UV-C in DG75 cells, as well as basal JNK-activity in HEK293 cells [14].
  • Nor does it inhibit MAP kinase kinase (MEK) and MAP kinase-activated protein (MAPKAP) kinase-2, the two enzymes immediately upstream and downstream, respectively, of ERK [27].
  • The NO donor SIN-1 inhibits in a concentration-dependent manner iNOS activity, and the effect is potentiated by NIC [28].
  • Under the same conditions, koningic acid also inhibited basal and SNP- SNAP-, and SIN-1-stimulated NAD-dependent modification of GAPDH and its enzymatic activity [23].
  • Although autocrine production of insulin-like growth factor 1 (IGF-1) promotes chondrocyte survival, pretreatment with IGF-1 could not prevent the cell death induced by SIN-1 exposure [21].

Other interactions of MAPKAP1


Analytical, diagnostic and therapeutic context of MAPKAP1

  • SIN-1 reduces platelet adhesion and platelet-thrombus formation following experimental angioplasty [1].
  • An additional control group of pigs received trimetaphan (n = 4), which induced hemodynamic changes similar to those that followed treatment with SIN-1 [1].
  • Scanning electron microscopy confirmed that platelets were deposited in the form of an adherent monolayer following superficial endothelial denudation and were reduced in number following treatment with SIN-1 [1].
  • The results indicate that 3-(4-morpholinyl)-sydnonimine (SIN-1, an O2*- and NO* donor) and chemically synthesized peroxynitrite, but not S-nitroso-N-acetyl-D,L-penicillamine (SNAP, an NO* donor), have a strong apoptotic effect on human thymocytes (annexin V staining and TUNEL reaction) [32].
  • Using immunoprecipitation and ESI-MS, we were also able to isolate and positively identify S-nitrosylated and nitrated mitochondrial ICDH from SIN-1-treated U937 cells as well as liver from ethanol-fed rats [33].


  1. SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty. Groves, P.H., Lewis, M.J., Cheadle, H.A., Penny, W.J. Circulation (1993) [Pubmed]
  2. Bidirectional regulation of osteoclast function by nitric oxide synthase isoforms. Brandi, M.L., Hukkanen, M., Umeda, T., Moradi-Bidhendi, N., Bianchi, S., Gross, S.S., Polak, J.M., MacIntyre, I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Neuronal differentiation and protection from nitric oxide-induced apoptosis require c-Jun-dependent expression of NCAM140. Feng, Z., Li, L., Ng, P.Y., Porter, A.G. Mol. Cell. Biol. (2002) [Pubmed]
  4. Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cobbs, C.S., Whisenhunt, T.R., Wesemann, D.R., Harkins, L.E., Van Meir, E.G., Samanta, M. Cancer Res. (2003) [Pubmed]
  5. Activation of mitogen-activated protein kinase associated with prostate cancer progression. Gioeli, D., Mandell, J.W., Petroni, G.R., Frierson, H.F., Weber, M.J. Cancer Res. (1999) [Pubmed]
  6. Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction. Stief, C.G., Holmquist, F., Djamilian, M., Krah, H., Andersson, K.E., Jonas, U. J. Urol. (1992) [Pubmed]
  7. SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity. Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S.Y., Huang, Q., Qin, J., Su, B. Cell (2006) [Pubmed]
  8. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Roux, P.P., Blenis, J. Microbiol. Mol. Biol. Rev. (2004) [Pubmed]
  9. Nitric oxide regulates the calcium current in isolated human atrial myocytes. Kirstein, M., Rivet-Bastide, M., Hatem, S., Bénardeau, A., Mercadier, J.J., Fischmeister, R. J. Clin. Invest. (1995) [Pubmed]
  10. Increased cytotoxicity of 3-morpholinosydnonimine to HepG2 cells in the presence of superoxide dismutase. Role of hydrogen peroxide and iron. Gergel, D., Misík, V., Ondrias, K., Cederbaum, A.I. J. Biol. Chem. (1995) [Pubmed]
  11. Protection against the co-operative toxicity of nitric oxide and oxygen free radicals by overexpression of antioxidant enzymes in bioengineered insulin-producing RINm5F cells. Tiedge, M., Lortz, S., Munday, R., Lenzen, S. Diabetologia (1999) [Pubmed]
  12. Differential mechanisms of nitric oxide- and peroxynitrite-induced cell death. Meij, J.T., Haselton, C.L., Hillman, K.L., Muralikrishnan, D., Ebadi, M., Yu, L. Mol. Pharmacol. (2004) [Pubmed]
  13. Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite. Thomas, S.R., Davies, M.J., Stocker, R. Chem. Res. Toxicol. (1998) [Pubmed]
  14. The human stress-activated protein kinase-interacting 1 gene encodes JNK-binding proteins. Schroder, W., Bushell, G., Sculley, T. Cell. Signal. (2005) [Pubmed]
  15. Alternative polyadenylation and splicing of mRNAs transcribed from the human Sin1 gene. Schroder, W., Cloonan, N., Bushell, G., Sculley, T. Gene (2004) [Pubmed]
  16. Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B-cell precursors. Madsen, P.S., Hokland, P., Clausen, N., Ellegaard, J., Hokland, M. Blood (1995) [Pubmed]
  17. Nuclear export of phosphorylated C/EBPbeta mediates the inhibition of albumin expression by TNF-alpha. Buck, M., Zhang, L., Halasz, N.A., Hunter, T., Chojkier, M. EMBO J. (2001) [Pubmed]
  18. Sympathetic stimulation overrides flow-mediated endothelium-dependent epicardial coronary vasodilation in transplant patients. Aptecar, E., Dupouy, P., Benvenuti, C., Mazzucotelli, J.P., Teiger, E., Geschwind, H., Castaigne, A., Loisance, D., Dubois-Rande, J.L. Circulation (1996) [Pubmed]
  19. Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins. Lüscher, T.F., Yang, Z., Tschudi, M., von Segesser, L., Stulz, P., Boulanger, C., Siebenmann, R., Turina, M., Bühler, F.R. Circ. Res. (1990) [Pubmed]
  20. Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress. Aguirre, T., Van Den Bosch, L., Goetschalckx, K., Tilkin, P., Mathijs, G., Cassiman, J.J., Robberecht, W. Ann. Neurol. (1998) [Pubmed]
  21. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Carlo, M.D., Loeser, R.F. Arthritis Rheum. (2003) [Pubmed]
  22. gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Christen, S., Woodall, A.A., Shigenaga, M.K., Southwell-Keely, P.T., Duncan, M.W., Ames, B.N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  23. Glyceraldehyde-3-phosphate dehydrogenase is required for the transport of nitric oxide in platelets. McDonald, B., Reep, B., Lapetina, E.G., Molina y Vedia, L. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  24. Metabolism of glyceryl trinitrate to nitric oxide by endothelial cells and smooth muscle cells and its induction by Escherichia coli lipopolysaccharide. Salvemini, D., Mollace, V., Pistelli, A., Anggard, E., Vane, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  25. Peroxynitrite induces HO-1 expression via PI3K/Akt-dependent activation of NF-E2-related factor 2 in PC12 cells. Li, M.H., Cha, Y.N., Surh, Y.J. Free Radic. Biol. Med. (2006) [Pubmed]
  26. Nitric oxide and peroxynitrite promote complete disruption of the [4Fe-4S] cluster of recombinant human iron regulatory protein 1. Soum, E., Drapier, J.C. J. Biol. Inorg. Chem. (2003) [Pubmed]
  27. In vitro inhibition of MAP kinase (ERK1/ERK2) activity by phosphorylated glia maturation factor (GMF). Zaheer, A., Lim, R. Biochemistry (1996) [Pubmed]
  28. Protection from nicotinamide inhibition of interleukin-1 beta-induced RIN cell nitric oxide formation is associated with induction of MnSOD enzyme activity. Andrade, J., Conde, M., Ramírez, R., Monteseirín, J., Conde, J., Sobrino, F., Bedoya, F.J. Endocrinology (1996) [Pubmed]
  29. Activation of MAP kinase-activated protein kinase 2 in human neutrophils after phorbol ester or fMLP peptide stimulation. Zu, Y.L., Ai, Y., Gilchrist, A., Labadia, M.E., Sha'afi, R.I., Huang, C.K. Blood (1996) [Pubmed]
  30. Nitric oxide regulates shear stress-induced early growth response-1. Expression via the extracellular signal-regulated kinase pathway in endothelial cells. Chiu, J.J., Wung, B.S., Hsieh, H.J., Lo, L.W., Wang, D.L. Circ. Res. (1999) [Pubmed]
  31. Ethanol metabolism alters interferon gamma signaling in recombinant HepG2 cells. Osna, N.A., Clemens, D.L., Donohue, T.M. Hepatology (2005) [Pubmed]
  32. In vivo and in vitro apoptosis of human thymocytes are associated with nitrotyrosine formation. Moulian, N., Truffault, F., Gaudry-Talarmain, Y.M., Serraf, A., Berrih-Aknin, S. Blood (2001) [Pubmed]
  33. Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury. Lee, J.H., Yang, E.S., Park, J.W. J. Biol. Chem. (2003) [Pubmed]
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