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Gene Review

Pdap1  -  PDGFA associated protein 1

Rattus norvegicus

Synonyms: 28 kDa heat-and acid-stable phosphoprotein, Haspp28, PAP, PAP1, PDGF-associated protein, ...
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Disease relevance of Pdap1

  • CONCLUSIONS: These observations show that the accumulated PAP into the acinar cells in response to acute pancreatitis behaves like all the other secretory proteins with the exception that it also accumulates in a new fibrillous cellular structure also found in the acinar lumen [1].
  • Apoptosis in the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma was studied during the post castration period of 14 days and compared with the ventral prostate [2].
  • Prostatic acid phosphatase (PAP) is uniquely expressed in prostatic tissue and prostate cancer [3].
  • In contrast, immunization with recombinant vaccinia expressing human PAP, but not rat PAP, generates a CTL response and tissue-specific prostatitis in the absence of detectable PAP-specific Abs [3].
  • These findings suggest that a cellular immune response to PAP, rather than Abs, mediates destructive autoimmune prostatitis [3].

High impact information on Pdap1


Chemical compound and disease context of Pdap1

  • Rats transplanted with the androgen-sensitive Dunning R3327 PAP prostatic adenocarcinoma were castrated and treated with either estrogen or vehicle alone for short periods (4 hr, 12 hr, 24 hr) and for 6 weeks [6].
  • The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc) [7].
  • In addition, the fMLP-induced lung weight gain of 9 +/- 7 g in the controls was prevented by pretreatment with PAP after 150 min in either concentration [8].
  • Treatment with PAP alone in either concentration did not induce any changes in mean pulmonary artery pressure, weight gain, or thromboxane A2 release [8].
  • A cell-by-cell analysis of the magnocellular elements in hypothalami of fifty Long-Evans (normal) and Brattleboro (diabetes insipidus) rats was done using the unlabeled antibody enzyme technique (PAP) with primary antisera directed against oxytocin (OXY), vasopressin (ADH), and the neurophysins [9].

Biological context of Pdap1

  • The protein copurified with platelet-derived growth factor (PDGF)-A and was therefore termed PDGF-associated protein (PAP). cDNAs corresponding to the protein were characterized from both rat and human cDNA libraries [10].
  • Antiapoptotic mechanisms are mediated by NF-kappaB and MAP kinases, and PAP I is one of the effectors of apoptosis inhibition [4].
  • It is suggested that one initial event during the androgen-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate [11].
  • We have previously demonstrated that serum factors from rats with acute pancreatitis, but not from healthy rats, could induce endogenous PAP I gene expression in the acinar cell line AR-42J (Dusetti, N., Mallo, G., Dagorn, J.-C., Iovanna, J. L. (1994) Biochem. Biophys. Res. Commun. 204, 238-243) [12].
  • In contrast, we found phosphorylation and nuclear translocation of STAT3 and induction of suppressor of cytokine signaling 3 in response to PAP I exposure [13].

Anatomical context of Pdap1

  • Important functional similarities to the anti-inflammatory cytokine IL-10 suggest that PAP I could play a role similar to that of IL-10 in epithelial cells [13].
  • Lectin binding was detected by polyclonal antibodies using PAP staining to the surface and the parietal cell region of the stomach, the brush border epithelium of the small intestine and to the surface membrane of the caecum and colon [14].
  • Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases [15].
  • Significant increases in P-selectin expression, neutrophil infiltration, and oxidative stress revealed that PAP treatment induced lung inflammation in rats and exacerbated inflammation in animals with pancreatitis [16].
  • Interestingly, PAPP-A expression in isolated CGCs was also strongly induced by FSH, and the induction was inhibited by added oocytes [17].

Associations of Pdap1 with chemical compounds

  • The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology [11].
  • PLD hydrolyzes phosphatidylcholine to choline and phosphatidic acid (PA), which is further metabolized to diacylglycerol (DG) by PA phosphohydrolase (PAP) [5].
  • ATPDA was a time-dependent irreversible inhibitor of the recombinant AST IV, and this inhibition was prevented by including either PAPS or adenosine 3',5'-diphosphate (PAP) in the incubation of AST IV with ATPDA [18].
  • IL-6 and dexamethasone together induced a marked stimulation of PAP I gene transcription, and this effect was slightly attenuated by IL-1 [12].
  • Tumor necrosis factor alpha induced an increase in PAP I mRNA expression, and interferon gamma caused an even greater increase in PAP I mRNA level [12].

Regulatory relationships of Pdap1


Other interactions of Pdap1


Analytical, diagnostic and therapeutic context of Pdap1

  • Pancreata prepared for light and electron microscopy were used for amylase and PAP detection with specific antibodies [1].
  • Thus, xenogeneic forms of PAP are a new tool for the induction of prostate-specific immunity and may prove useful for the immunotherapy of prostate cancer [3].
  • Levels of reg I/PSP and reg III/PAP were estimated by enzyme-linked immunosorbent assay [21].
  • PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators [15].
  • By in situ hybridization, ovary PAPP-A mRNA was markedly increased by pregnant mare serum gonadotropin treatment, and the message was localized to the membrana GCs but not cumulus GCs (CGCs) of dominant follicles [17].


  1. Localization of rat pancreatitis-associated protein during bile salt-induced pancreatitis. Morisset, J., Iovanna, J., Grondin, G. Gastroenterology (1997) [Pubmed]
  2. Castration induces apoptosis in the ventral prostate but not in an androgen-sensitive prostatic adenocarcinoma in the rat. Brändström, A., Westin, P., Bergh, A., Cajander, S., Damber, J.E. Cancer Res. (1994) [Pubmed]
  3. Induction of tissue-specific autoimmune prostatitis with prostatic acid phosphatase immunization: implications for immunotherapy of prostate cancer. Fong, L., Ruegg, C.L., Brockstedt, D., Engleman, E.G., Laus, R. J. Immunol. (1997) [Pubmed]
  4. Tumor necrosis factor alpha triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation. Malka, D., Vasseur, S., Bödeker, H., Ortiz, E.M., Dusetti, N.J., Verrando, P., Dagorn, J.C., Iovanna, J.L. Gastroenterology (2000) [Pubmed]
  5. Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes mediates the expressions of c-jun and c-fos: involvement of protein tyrosine kinase, protein kinase C, and Ca2+. Adachi, T., Nakashima, S., Saji, S., Nakamura, T., Nozawa, Y. Hepatology (1996) [Pubmed]
  6. Estrogen induces apoptosis in a rat prostatic adenocarcinoma: association with an increased expression of TGF-beta 1 and its type-I and type-II receptors. Landström, M., Eklöv, S., Colosetti, P., Nilsson, S., Damber, J.E., Bergh, A., Funa, K. Int. J. Cancer (1996) [Pubmed]
  7. Blockade of dopamine receptors explains the lack of 5-HT stereotypy on treatment with the putative 5-HT1A agonist LY165163. Donohoe, T.P., Hutson, P.H., Curzon, G. Psychopharmacology (Berl.) (1987) [Pubmed]
  8. Pancreatitis-associated protein protects the lung from leukocyte-induced injury. Heller, A., Fiedler, F., Schmeck, J., Lück, V., Iovanna, J.L., Koch, T. Anesthesiology (1999) [Pubmed]
  9. Immunohistochemical analysis of magnocellular elements in rat hypothalamus: distribution and numbers of cells containing neurophysin, oxytocin, and vasopressin. Rhodes, C.H., Morrell, J.I., Pfaff, D.W. J. Comp. Neurol. (1981) [Pubmed]
  10. Characterization of a novel platelet-derived growth factor-associated protein. Fischer, W.H., Schubert, D. J. Neurochem. (1996) [Pubmed]
  11. Prostatic tumor regrowth after initially successful castration therapy may be related to a decreased apoptotic cell death rate. Landström, M., Damber, J.E., Bergh, A. Cancer Res. (1994) [Pubmed]
  12. Pancreatitis-associated protein I (PAP I), an acute phase protein induced by cytokines. Identification of two functional interleukin-6 response elements in the rat PAP I promoter region. Dusetti, N.J., Ortiz, E.M., Mallo, G.V., Dagorn, J.C., Iovanna, J.L. J. Biol. Chem. (1995) [Pubmed]
  13. Pancreatitis-associated protein I suppresses NF-kappa B activation through a JAK/STAT-mediated mechanism in epithelial cells. Folch-Puy, E., Granell, S., Dagorn, J.C., Iovanna, J.L., Closa, D. J. Immunol. (2006) [Pubmed]
  14. Reversible effect of phytohaemagglutinin on the growth and metabolism of rat gastrointestinal tract. Bardocz, S., Grant, G., Ewen, S.W., Duguid, T.J., Brown, D.S., Englyst, K., Pusztai, A. Gut (1995) [Pubmed]
  15. Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Schmitz, A., Sankaranarayanan, A., Azam, P., Schmidt-Lassen, K., Homerick, D., Hänsel, W., Wulff, H. Mol. Pharmacol. (2005) [Pubmed]
  16. The pancreatitis-associated protein induces lung inflammation in the rat through activation of TNFalpha expression in hepatocytes. Folch-Puy, E., García-Movtero, A., Iovanna, J.L., Dagorn, J.C., Prats, N., Vaccaro, M.I., Closa, D. J. Pathol. (2003) [Pubmed]
  17. Pregnancy-associated plasma protein-a production in rat granulosa cells: stimulation by follicle-stimulating hormone and inhibition by the oocyte-derived bone morphogenetic protein-15. Matsui, M., Sonntag, B., Hwang, S.S., Byerly, T., Hourvitz, A., Adashi, E.Y., Shimasaki, S., Erickson, G.F. Endocrinology (2004) [Pubmed]
  18. Affinity labeling of aryl sulfotransferase IV. Identification of a peptide sequence at the binding site for 3'-phosphoadenosine-5'-phosphosulfate. Zheng, Y., Bergold, A., Duffel, M.W. J. Biol. Chem. (1994) [Pubmed]
  19. Transforming growth factor beta increases the activity of phosphatidate phosphohydrolase-1 in rat hepatocytes. Dixon, M.C., Yeaman, S.J., Agius, L., Day, C.P. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  20. Differentially expressed genes in hippocampal cell cultures in response to an excitotoxic insult by quinolinic acid. Seidel, B., Keilhoff, G., Reinheckel, T., Wolf, G. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  21. Comparison of reg I and reg III levels during acute pancreatitis in the rat. Zenilman, M.E., Tuchman, D., Zheng, Q., Levine, J., Delany, H. Ann. Surg. (2000) [Pubmed]
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