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Gene Review

MZB1  -  marginal zone B and B1 cell-specific protein

Homo sapiens

Synonyms: HSPC190, MEDA-7, MEDA7, MGC29506, Marginal zone B-and B1-cell-specific protein, ...
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Disease relevance of MGC29506

  • In four of the neuroblastoma cell lines, VIP and PACAP stimulated cyclic AMP production with different potencies and levels of maximal stimulation [1].
  • Pituitary adenylate cyclase-activating peptide 38 (PACAP 38) is a neuropeptide that displays several biological effects of interest in the context of airway diseases such as asthma and chronic obstructive pulmonary disease [2].
  • Co-treatment with neutralizing antiserum to RANTES attenuated PACAP-mediated protection from toxicity associated with gp120 [3].
  • Since this year, using three models of disease, septic shock, rheumathoid arthritis, and Crohn's disease, we are trying to contribute with new pieces to the puzzle of immunity to approach the use of VIP/PACAP system as a therapeutic agent [4].
  • The effect of PACAP 38 administration on neuroendocrine and immune parameters was examined in rats with LPS-induced peritonitis [5].

Psychiatry related information on MGC29506

  • However, PACAP effectively ameliorated behavioral symptoms in all groups, with a degree of recovery depending on age and endocrine status [6].

High impact information on MGC29506

  • In this issue of the JCI, Lang et al. demonstrate that overexpression of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I (PAC1) receptor gene results in abnormal development of the SCO and vel cells, leading to congenital hydrocephalus (see the related article beginning on page 1924) [7].
  • Here we report the cloning, by the yeast two hybrid system with dominant negative caspase-2 as "bait," of a proapoptotic molecule named proapoptotic caspase adaptor protein (PACAP), encoded by a 372-base pair open reading frame [8].
  • Northern blot analysis revealed gene expression for only the PACAP-preferring (PAC1) receptor [9].
  • Consistent with this notion, we determined that the most BrdU positive NPCs differentiated to astrocytes through PAC1 signaling [10].
  • It has been well established that the PACAP/PAC1 system induces differentiation of neural progenitor cells (NPCs) through the Gs-mediated cAMP-dependent signaling pathway [10].

Chemical compound and disease context of MGC29506


Biological context of MGC29506


Anatomical context of MGC29506

  • Activation of the cAMP/protein kinase A pathway in Caco-2 cell monolayers either using pharmacological tools (forskolin, 8-br-cAMP, [(11,22,28)Ala]VIP) or physiological activators (the neuropeptides VIP and PACAP) inhibited hPAT1 function (beta-alanine uptake) at the apical membrane [16].
  • We report that in freshly isolated human monocytes PACAP acts as a pro-inflammatory molecule [17].
  • Likewise, high numbers of NOS- and PACAP-containing nerve cell bodies were seen in both ganglia [18].
  • Our research about VIP/PACAP and the immune system goes back to 1990 when our group described the expression of VIP on lymphocytes for the first time [4].
  • These data demonstrate that chVIP, PACAP, and to a lesser extent helodermin were capable of potently stimulating cAMP generation in the avian central nervous system [19].

Associations of MGC29506 with chemical compounds

  • At 37 degrees C PACAP transiently increased cAMP levels in the presence of the non-specific phosphodiesterase inhibitor IBMX, suggesting rapid desensitization [20].
  • The differential effects of PACAP peptides on SCG NPY and catecholamine content and secretion coincided with previous studies that activated directly the sympathetic intracellular cyclic AMP-protein kinase A signaling pathway [21].
  • This is accompanied by a dramatic switch in the expression of receptors for the structurally related neuropeptides VIP (vasoactive intestinal polypeptide) and PACAP (pituitary adenylate cyclase activating polypeptide) [22].
  • When administered together with LPS, PACAP 38 reversed its effect on immune and humoral parameters, causing a decrease in the serum concentrations of TNFalpha and corticosterone, and an increase in T4 and GH [5].
  • Dopamine (100 microM), PACAP (50 nM) and forskolin (10 microM) induced a 50-, 30- and 40-fold cAMP accumulation on glial cells, respectively, but not ip3 production [23].

Regulatory relationships of MGC29506

  • Administration of the beta-adrenoreceptor agonist isoproterenol mimicked the stimulatory effect of PACAP on both steroid secretion whereas preincubation of fetal cells with the beta-adrenoreceptor antagonist propranolol suppressed the steroidogenic effect of PACAP [24].

Other interactions of MGC29506


Analytical, diagnostic and therapeutic context of MGC29506


  1. Characterization of novel splice variants of the PAC1 receptor in human neuroblastoma cells: consequences for signaling by VIP and PACAP. Lutz, E.M., Ronaldson, E., Shaw, P., Johnson, M.S., Holland, P.J., Mitchell, R. Mol. Cell. Neurosci. (2006) [Pubmed]
  2. Pituitary adenylate cyclase-activating peptide inhibits neutrophil chemotaxis. Kinhult, J., Uddman, R., Laan, M., Lindén, A., Cardell, L.O. Peptides (2001) [Pubmed]
  3. Chemokine release is associated with the protective action of PACAP-38 against HIV envelope protein neurotoxicity. Brenneman, D.E., Hauser, J.M., Spong, C., Phillips, T.M. Neuropeptides (2002) [Pubmed]
  4. VIP-PACAP system in immunity: new insights for multitarget therapy. Gomariz, R.P., Juarranz, Y., Abad, C., Arranz, A., Leceta, J., Martinez, C. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  5. PACAP 38 as a modulator of immune and endocrine responses during LPS-induced acute inflammation in rats. Bik, W., Wolinska-Witort, E., Pawlak, J., Skwarlo-Sonta, K., Chmielowska, M., Martynska, L., Baranowska-Bik, A., Baranowska, B. J. Neuroimmunol. (2006) [Pubmed]
  6. Comparative study of the effects of PACAP in young, aging, and castrated males in a rat model of Parkinson's disease. Reglódi, D., Tamás, A., Lengvári, I., Toth, G., Szalontay, L., Lubics, A. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  7. Neuropeptide signaling and hydrocephalus: SCO with the flow. Picketts, D.J. J. Clin. Invest. (2006) [Pubmed]
  8. Characterization of a novel proapoptotic caspase-2- and caspase-9-binding protein. Bonfoco, E., Li, E., Kolbinger, F., Cooper, N.R. J. Biol. Chem. (2001) [Pubmed]
  9. Differential effects of peptide histidine isoleucine (PHI) and related peptides on stimulation and suppression of neuroblastoma cell proliferation. A novel VIP-independent action of PHI via MAP kinase. Lelièvre, V., Pineau, N., Du, J., Wen, C.H., Nguyen, T., Janet, T., Muller, J.M., Waschek, J.A. J. Biol. Chem. (1998) [Pubmed]
  10. PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells. Nishimoto, M., Furuta, A., Aoki, S., Kudo, Y., Miyakawa, H., Wada, K. Glia (2007) [Pubmed]
  11. MGC29506 gene, frequently down-regulated in intestinal-type gastric cancer, encodes secreted-type protein with conserved cysteine residues. Katoh, M., Katoh, M. Int. J. Oncol. (2003) [Pubmed]
  12. Contrasting effects of PACAP and carbachol on [Ca2+]i and inositol phosphates in human neuroblastoma NB-OK-1 cells. Delporte, C., Van Praet, A., Herchuelz, A., Winand, J., Christophe, J. Peptides (1993) [Pubmed]
  13. Human A-type ANP receptor upregulation by PACAP and carbachol in neuroblastoma cells. Forgeur, A., Svoboda, M., Winand, J., Robberecht, P., Delporte, C. Mol. Cell. Endocrinol. (1999) [Pubmed]
  14. Mechanisms and modulation of pituitary adenylate cyclase-activating protein-induced calcium mobilization in human neutrophils. Harfi, I., Sariban, E. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  15. Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta. Scaldaferri, M.L., Modesti, A., Palumbo, C., Ulisse, S., Fabbri, A., Piccione, E., Frajese, G., Moretti, C. Endocrinology (2000) [Pubmed]
  16. Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1). Anderson, C.M., Thwaites, D.T. J. Cell. Physiol. (2005) [Pubmed]
  17. The neuropeptide pituitary adenylate cyclase activating protein is a physiological activator of human monocytes. El Zein, N., Corazza, F., Sariban, E. Cell. Signal. (2006) [Pubmed]
  18. Neuronal messengers and peptide receptors in the human sphenopalatine and otic ganglia. Uddman, R., Tajti, J., Möller, S., Sundler, F., Edvinsson, L. Brain Res. (1999) [Pubmed]
  19. Cyclic AMP formation in chicken brain: effect of vasoactive intestinal peptide, peptide histidine-isoleucine (PHI), and some PHI-related peptides. Dejda, A., Matczak, I., Wiktorowska-Owczarek, A., Nowak, J.Z. Polish journal of pharmacology. (2003) [Pubmed]
  20. Characterization of functional VIP/PACAP receptors in the human erythroleukemic HEL cell line. Lema-Kisoka, R., Hayez, N., Langer, I., Robberecht, P., Sariban, E., Delporte, C. Peptides (2001) [Pubmed]
  21. Pituitary adenylate cyclase-activating polypeptides, PACAP-38 and PACAP-27, regulation of sympathetic neuron catecholamine, and neuropeptide Y expression through activation of type I PACAP/VIP receptor isoforms. Braas, K.M., May, V. Ann. N. Y. Acad. Sci. (1996) [Pubmed]
  22. Switches in the expression and function of PACAP and VIP receptors during phenotypic interconversion in human neuroblastoma cells. Lelièvre, V., Becq-Giraudon, L., Meunier, A.C., Muller, J.M. Neuropeptides (1996) [Pubmed]
  23. Expression of functional receptors and transmitter enzymes in cultured Muller cells. Kubrusly, R.C., da Cunha, M.C., Reis, R.A., Soares, H., Ventura, A.L., Kurtenbach, E., de Mello, M.C., de Mello, F.G. Brain Res. (2005) [Pubmed]
  24. Occurrence and effect of PACAP in the human fetal adrenal gland. Breault, L., Yon, L., Montéro, M., Chouinard, L., Contesse, V., Delarue, C., Fournier, A., Lehoux, J.G., Vaudry, H., Gallo-Payet, N. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  25. Sequence and expression of a cDNA encoding both pituitary adenylate cyclase activating polypeptide and growth hormone-releasing hormone in grouper (Epinephelus coioides). Jiang, Y., Li, W.S., Xie, J., Lin, H.R. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (2003) [Pubmed]
  26. Human PACAP response gene 1 (p22/PRG1): proliferation-associated expression in pancreatic carcinoma cells. Schäfer, H., Lettau, P., Trauzold, A., Banasch, M., Schmidt, W.E. Pancreas (1999) [Pubmed]
  27. The circadian photopigment melanopsin is expressed in the blind subterranean mole rat, Spalax. Hannibal, J., Hindersson, P., Nevo, E., Fahrenkrug, J. Neuroreport (2002) [Pubmed]
  28. Characterization and messenger ribonucleic acid distribution of a cloned pituitary adenylate cyclase-activating polypeptide type I receptor in the frog Xenopus laevis brain. Hu, Z., Lelievre, V., Chao, A., Zhou, X., Waschek, J.A. Endocrinology (2000) [Pubmed]
  29. PAC1-R null isoform expression in human prostate cancer tissue. Mammi, C., Frajese, G.V., Vespasiani, G., Mariani, S., Gnessi, L., Farini, D., Fabbri, A., Frajese, G., Moretti, C. Prostate (2006) [Pubmed]
  30. The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers. Birk, S., Sitarz, J.T., Petersen, K.A., Oturai, P.S., Kruuse, C., Fahrenkrug, J., Olesen, J. Regul. Pept. (2007) [Pubmed]
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