13 dibutyrate phorbol 12


Summary: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.

Top Publications

  1. Ren C, Zhang J, Philipson K, Kotlikoff M, Blaustein M, Matteson D. Activation of L-type Ca2+ channels by protein kinase C is reduced in smooth muscle-specific Na+/Ca2+ exchanger knockout mice. Am J Physiol Heart Circ Physiol. 2010;298:H1484-91 pubmed publisher
    ..We conclude that in NCX1(SM-/-) myocytes, reduced Ca(2+) entry via NCX1 lowers cytosolic [Ca(2+)], thereby reducing PKC activation that lowers LVGC activation...
  2. Yang H, Kim J, Lee K, Jang Y. Rac/ROS-related protein kinase C and phosphatidylinositol-3-kinase signaling are involved in a negative regulating cascade in B cell activation by antibody-mediated cross-linking of MHC class II molecules. Mol Immunol. 2010;47:706-12 pubmed publisher
    ..Collectively, Rac/ROS-related PKC and PI3K signaling are involved in a negative regulation cascade through the cross-linking of MHC class II molecules by anti-MHC class II antibodies in resting B cells. ..
  3. Sakai H, Kurihara Y, Hashimoto Y, Chiba Y, Misawa M. Phorbol 12,13-dibutyrate-mediated contraction of the stimulated bronchial smooth muscles of mice. Respir Physiol Neurobiol. 2010;173:120-4 pubmed publisher
    ..Thus, a certain level of intracellular Ca(2+) might be needed both for an activation of CPI-17 and an induction of contraction induced by PDBu in mouse BSMs. ..
  4. Black J, Dykes A, Thatcher S, Brown D, Bryda E, Wright G. FRET analysis of actin-myosin interaction in contracting rat aortic smooth muscle. Can J Physiol Pharmacol. 2009;87:327-36 pubmed publisher
    ..The results provide direct evidence of dynamic remodeling of the contractile protein during vascular smooth muscle contraction and suggest that FRET analysis may be a powerful tool for assessment of tissue protein-protein associations. ..
  5. Dewing P, Christensen A, Bondar G, Micevych P. Protein kinase C signaling in the hypothalamic arcuate nucleus regulates sexual receptivity in female rats. Endocrinology. 2008;149:5934-42 pubmed publisher
    ..Together these findings indicate that rapid membrane ERalpha-mGluR1a interactions activate PKCtheta cell signaling, which regulates female sexual receptivity. ..
  6. Lin P, Tsai M, Lu G, Lu D, Chuang C, Yang H, et al. Ecstasy and methamphetamine elicit action potential bursts via different mechanisms in a central snail neuron. Neurotoxicology. 2010;31:26-41 pubmed publisher
    ..Rather, action potential bursts may be elicited through (1) combined activation of the cAMP-PKA signaling pathway and inhibition of the I(KD) and (2) combined activation of PKC and inhibition of the I(KD)...
  7. Wang H, Yu Y, Liao W, Wang Z, Lv Y, Zhang Y, et al. Negative regulation of endogenous protein kinase Calpha on the dynamic change of carbachol-induced intracellular calcium response in different melanoma cells. J Cell Physiol. 2009;221:276-82 pubmed publisher
    ..The functional analysis on the relationship between CCh-induced calcium response and endogenous PKCalpha expression might be helpful to predict the development of melanoma. ..
  8. Sosa M, Lewin N, Choi S, Blumberg P, Kazanietz M. Biochemical characterization of hyperactive beta2-chimaerin mutants revealed an enhanced exposure of C1 and Rac-GAP domains. Biochemistry. 2009;48:8171-8 pubmed publisher
    ..These studies suggest that beta2-chimaerin must undergo a conformational rearrangement in order to expose its lipid binding sites and become activated. ..
  9. Karasu A, Aras Y, Sabanci P, Sa─člam G, Izgi N, Biltekin B, et al. The effects of protein kinase C activator phorbol dibutyrate on traumatic brain edema and aquaporin-4 expression. Ulus Travma Acil Cerrahi Derg. 2010;16:390-4 pubmed
    ..05). This study showed that traumatic brain edema was prevented by intravenous PDBu administration via AQP4 downregulation, supporting the idea emphasizing the importance of AQP4 expression control in TBI. ..

More Information


  1. Bie B, Zhang Y, Zhao Z. Inhibition of P2X receptor-mediated inward current by protein kinase C in small-diameter dorsal root ganglion neurons of adult rats. Neurosci Bull. 2009;25:179-86 pubmed publisher
    ..Activation of PKC negatively modulated the P2X receptor-mediated currents in rat DRG neurons, which may be of benefit to preventing the over-excitation of nociceptor under inflammatory or neuropathic conditions. ..
  2. Gobbi G, Mirandola P, Carubbi C, Micheloni C, Malinverno C, Lunghi P, et al. Phorbol ester-induced PKCepsilon down-modulation sensitizes AML cells to TRAIL-induced apoptosis and cell differentiation. Blood. 2009;113:3080-7 pubmed publisher
    ..We believe that the use of TRAIL in combination with phorbol esters (or possibly more specific PKCepsilon down-modulators) might represent a significative improvement of our therapeutic arsenal against AML. ..
  3. Goyal R, Mittal A, Chu N, Shi L, Zhang L, Longo L. Maturation and the role of PKC-mediated contractility in ovine cerebral arteries. Am J Physiol Heart Circ Physiol. 2009;297:H2242-52 pubmed publisher
    ..Overall, the present study demonstrates an important maturational shift from RhoA/ROCK-mediated to CPI-17/caldesmon-mediated PKC-induced contractile response in ovine cerebral arteries. ..
  4. Visigalli R, Barilli A, Parolari A, Sala R, Rotoli B, Bussolati O, et al. Regulation of arginine transport and metabolism by protein kinase Calpha in endothelial cells: stimulation of CAT2 transporters and arginase activity. J Mol Cell Cardiol. 2010;49:260-70 pubmed publisher
    ..This metabolic deviation may contribute to the endothelial dysfunction associated with conditions of PKC overactivity. ..
  5. Sugaya A, Takeoka M, Itano N, Taguchi A, Ehara T, Taniguchi S. Calponin h1-S175T point mutation enhances resistance to actin cytoskeleton perturbation in human cancer cells. Anticancer Res. 2010;30:1071-8 pubmed
    ..This result indicates that S175T may be an effective target for new cancer treatments. ..
  6. Basu A, Sridharan S, Persaud S. Regulation of protein kinase C delta downregulation by protein kinase C epsilon and mammalian target of rapamycin complex 2. Cell Signal. 2009;21:1680-5 pubmed publisher
    ..Depletion of PKC epsilon also enhanced PKC delta downregulation by PDBu. These results suggest that downregulation of PKC delta is regulated by PKC epsilon and mammalian target of rapamycin complex 2 (mTORC2). ..
  7. Xiao H, Bai X, Kapus A, Lu W, Mak A, Liu M. The protein kinase C cascade regulates recruitment of matrix metalloprotease 9 to podosomes and its release and activation. Mol Cell Biol. 2010;30:5545-61 pubmed publisher
    ..Our data suggest that multiple PKC isozymes form a signaling cascade that controls podosome formation and dynamics and MMP-9 recruitment, release, and activation in a coordinated fashion. ..
  8. Summers S, Hayashi Y, Nguyen S, Nguyen T, Purdy R. Hindlimb unweighting induces changes in the p38MAPK contractile pathway of the rat abdominal aorta. J Appl Physiol (1985). 2009;107:121-7 pubmed publisher
    ..The results of this study demonstrate that HLU downregulates p38(MAPK), but not ERK, signaling. In turn, this may decrease actin availability for contraction. ..
  9. Torres Marquez E, Sinnett Smith J, Guha S, Kui R, Waldron R, Rey O, et al. CID755673 enhances mitogenic signaling by phorbol esters, bombesin and EGF through a protein kinase D-independent pathway. Biochem Biophys Res Commun. 2010;391:63-8 pubmed publisher
  10. Gupte S, Kaminski P, George S, Kouznestova L, Olson S, Mathew R, et al. Peroxide generation by p47phox-Src activation of Nox2 has a key role in protein kinase C-induced arterial smooth muscle contraction. Am J Physiol Heart Circ Physiol. 2009;296:H1048-57 pubmed publisher
    ..Thus a p47(phox) and Src kinase activation of peroxide production by Nox2 appears to be an important contributor to vascular contractile mechanisms mediated through activation of PKC. ..
  11. Villareal G, Li Q, Cai D, Fink A, Lim T, Bougie J, et al. Role of protein kinase C in the induction and maintenance of serotonin-dependent enhancement of the glutamate response in isolated siphon motor neurons of Aplysia californica. J Neurosci. 2009;29:5100-7 pubmed publisher
  12. Anderson A, Child E, Prasad A, Elphick L, Mann D. Cyclin D1 and cyclin D3 show divergent responses to distinct mitogenic stimulation. J Cell Physiol. 2010;225:638-45 pubmed publisher
    ..These findings uncover additional levels of complexity in the regulation of the cell cycle at the level of the D-type cyclins and thus may have important therapeutic implications in cancers where specific D-cyclins are overexpressed. ..
  13. Hatou S, Yamada M, Mochizuki H, Nishida T. Role of protein kinase C in regulation of Na+- and K +-dependent ATPase activity and pump function in corneal endothelial cells. Jpn J Ophthalmol. 2009;53:235-42 pubmed publisher
  14. Chen J, De S, Damron D, Chen W, Hay N, Byzova T. Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice. Blood. 2004;104:1703-10 pubmed
    ..As a consequence of impaired alpha(IIb)beta(3) activation and platelet aggregation, Akt-1 null mice showed significantly longer bleeding times than wild-type mice. ..
  15. Chang C, Jiang X, Moulder K, Mennerick S. Rapid activation of dormant presynaptic terminals by phorbol esters. J Neurosci. 2010;30:10048-60 pubmed publisher
    ..These results suggest that the initial release competence of synapses can dictate the acute response to second messenger modulation, and the results suggest multiple pathways to presynaptic dormancy and awakening. ..
  16. Sathishkumar K, Yallampalli U, Elkins R, Yallampalli C. Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries. J Vasc Res. 2010;47:384-98 pubmed publisher
    ..The results indicate that Raf-1 kinase plays an important role in the regulation of vascular contractility through regulation of calcium sensitization. ..
  17. Wang J, Yin G, Menon P, Pang J, Smolock E, Yan C, et al. Phosphorylation of G protein-coupled receptor kinase 2-interacting protein 1 tyrosine 392 is required for phospholipase C-gamma activation and podosome formation in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2010;30:1976-82 pubmed publisher
    ..We propose that specific signaling modules are assembled in a GIT1 phosphotyrosine-dependent manner as exemplified by PLC? activation versus extracellular signal-regulated kinase 1/2 activation. ..
  18. Shaha S, Tomic J, Shi Y, Pham T, Mero P, White D, et al. Prolonging microtubule dysruption enhances the immunogenicity of chronic lymphocytic leukaemia cells. Clin Exp Immunol. 2009;158:186-98 pubmed publisher
    ..Use of PKC agonists and microtubule inhibitors to mimic TLR-signalling, and increase the immunogenicity of CLL cells, has implications for the design of chemo-immunotherapeutic strategies. ..
  19. Appel S, Allen P, Vetterkind S, Jin J, Morgan K. h3/Acidic calponin: an actin-binding protein that controls extracellular signal-regulated kinase 1/2 activity in nonmuscle cells. Mol Biol Cell. 2010;21:1409-22 pubmed publisher
    ..2 migration in an in vitro wound healing assay. Our findings are consistent with a model whereby h3/acidic calponin controls fibroblast migration by regulation of ERK1/2-mediated l-caldesmon phosphorylation. ..
  20. Zoer B, Blanco C, Villamor E. Role of Rho-kinase in mediating contraction of chicken embryo femoral arteries. J Comp Physiol B. 2010;180:427-35 pubmed publisher
    ..In summary, our findings are indicative of a role for Rho-kinase activity in depolarization- and agonist-induced force generation in chicken embryo femoral arteries...
  21. Bossuyt J, Despa S, Han F, Hou Z, Robia S, Lingrel J, et al. Isoform specificity of the Na/K-ATPase association and regulation by phospholemman. J Biol Chem. 2009;284:26749-57 pubmed publisher
    ..1 +/- 1.1 mm, respectively) but increased V(max) only for NKA-alpha2 (1.9 +/- 0.4 versus 1.2 +/- 0.5 mm/min). In conclusion, PLM associates with and modulates both NKA-alpha1 and NKA-alpha2 in a comparable but not identical manner. ..
  22. Chang K, Xiao D, Huang X, Longo L, Zhang L. Chronic hypoxia increases pressure-dependent myogenic tone of the uterine artery in pregnant sheep: role of ERK/PKC pathway. Am J Physiol Heart Circ Physiol. 2009;296:H1840-9 pubmed publisher
  23. Shibasaki M, Kurokawa K, Katsura M, Ohkuma S. Direct evidence for the up-regulation of Vps34 regulated by PKCgamma during short-term treatment with morphine. Synapse. 2009;63:365-8 pubmed publisher
    ..These results indicates that opioid receptor activation increases PKCgamma phosphorylation in the neurons and, in turn, upregulates Vps34 during short-term treatment with neurons. ..
  24. Zhang Y, Li W, Chi H, Chen J, DenBesten P. JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro. Matrix Biol. 2007;26:633-41 pubmed
    ..These in vitro findings suggest that c-Jun is a key regulatory element for MMP-20 expression, and human ameloblast lineage cells can respond to fluoride by down-regulating MMP-20 transcription through the JNK/c-Jun signaling pathway. ..
  25. Copel C, Osorio N, Crest M, Gola M, Delmas P, Clerc N. Activation of neurokinin 3 receptor increases Na(v)1.9 current in enteric neurons. J Physiol. 2009;587:1461-79 pubmed publisher
    ..9) by NK3r activation is also likely to amplify slow EPSPs generated in the IPANs. These changes in excitability potentially have a profound effect on the entire enteric synaptic circuit and ultimately on gut motility and secretion. ..