Gene Symbol: Prkd1
Description: protein kinase D1
Alias: Pkcm, Prkcm, nPKC-D1, nPKC-mu, serine/threonine-protein kinase D1, protein kinase C mu type
Species: rat
Products:     Prkd1

Top Publications

  1. Berna M, Hoffmann K, Tapia J, Thill M, Pace A, Mantey S, et al. CCK causes PKD1 activation in pancreatic acini by signaling through PKC-delta and PKC-independent pathways. Biochim Biophys Acta. 2007;1773:483-501 pubmed
    ..CCK stimulated translocation of total and phosphorylated PKD1 to the membrane. These results demonstrate that CCK(A) receptor activation leads to PKD activation by signaling through PKC-dependent and PKC-independent pathways. ..
  2. Steinbusch L, Dirkx E, Hoebers N, Roelants V, Foretz M, Viollet B, et al. Overexpression of AMP-activated protein kinase or protein kinase D prevents lipid-induced insulin resistance in cardiomyocytes. J Mol Cell Cardiol. 2013;55:165-73 pubmed publisher
    ..This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". ..
  3. Bisbal M, Conde C, Donoso M, Bollati F, Sesma J, Quiroga S, et al. Protein kinase d regulates trafficking of dendritic membrane proteins in developing neurons. J Neurosci. 2008;28:9297-308 pubmed publisher
    ..These results suggest that in neurons PKD1 regulates TGN-derived sorting of dendritic proteins and hence has a role in neuronal polarity. ..
  4. Cabrera Poch N, Sánchez Ruiloba L, Rodríguez Martínez M, Iglesias T. Lipid raft disruption triggers protein kinase C and Src-dependent protein kinase D activation and Kidins220 phosphorylation in neuronal cells. J Biol Chem. 2004;279:28592-602 pubmed
    ..Collectively, these results reveal the importance of lipid rafts on PKD activation, translocation, and downstream signaling to its substrate Kidins220. ..
  5. Iwata M, Maturana A, Hoshijima M, Tatematsu K, Okajima T, Vandenheede J, et al. PKCepsilon-PKD1 signaling complex at Z-discs plays a pivotal role in the cardiac hypertrophy induced by G-protein coupling receptor agonists. Biochem Biophys Res Commun. 2005;327:1105-13 pubmed
    ..Taken together, the PKCepsilon-PKD1 complex at Z-discs could play a pivotal role in the cardiac hypertrophy induced by GPCR agonists, at least alpha-adrenergic receptor agonist. ..
  6. Ha C, Wang W, Jhun B, Wong C, Hausser A, Pfizenmaier K, et al. Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem. 2008;283:14590-9 pubmed publisher
    ..These findings suggest that the PKD-HDAC5 pathway plays an important role in VEGF regulation of gene transcription and angiogenesis. ..
  7. Monovich L, Vega R, Meredith E, Miranda K, Rao C, Capparelli M, et al. A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase. FEBS Lett. 2010;584:631-7 pubmed publisher
    ..BPKDi blocks signal-dependent phosphorylation and nuclear export of class IIa HDACs in cardiomyocytes and concomitantly suppresses hypertrophy of these cells. These studies define PKD as a principal cardiac class IIa HDAC kinase. ..
  8. Liu D, Evans I, Britton G, Zachary I. The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis. Oncogene. 2008;27:2989-98 pubmed
  9. Storz P, Toker A. Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. EMBO J. 2003;22:109-20 pubmed
    ..We propose a model in which protection from oxidative stress-induced cell death requires the tyrosine phosphorylation of PKD leading to the activation of the transcription factor NF-kappaB. ..

More Information


  1. Storz P, Döppler H, Johannes F, Toker A. Tyrosine phosphorylation of protein kinase D in the pleckstrin homology domain leads to activation. J Biol Chem. 2003;278:17969-76 pubmed
    ..These data reveal a tyrosine phosphorylation-dependent activation mechanism for PKD and suggest that this event contributes to the release of the autoinhibitory PKD PH domain leading to kinase activation and downstream responses. ..
  2. Czöndör K, Ellwanger K, Fuchs Y, Lutz S, Gulyás M, Mansuy I, et al. Protein kinase D controls the integrity of Golgi apparatus and the maintenance of dendritic arborization in hippocampal neurons. Mol Biol Cell. 2009;20:2108-20 pubmed publisher
    ..Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons. ..
  3. Evans I, Britton G, Zachary I. Vascular endothelial growth factor induces heat shock protein (HSP) 27 serine 82 phosphorylation and endothelial tubulogenesis via protein kinase D and independent of p38 kinase. Cell Signal. 2008;20:1375-84 pubmed publisher
  4. Luiken J, Vertommen D, Coort S, Habets D, El Hasnaoui M, Pelsers M, et al. Identification of protein kinase D as a novel contraction-activated kinase linked to GLUT4-mediated glucose uptake, independent of AMPK. Cell Signal. 2008;20:543-56 pubmed publisher
  5. Eisenberg Lerner A, Kimchi A. PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk. Cell Death Differ. 2012;19:788-97 pubmed publisher
    ..Taken together, our results describe PKD as a novel Vps34 kinase that functions as an effecter of autophagy under oxidative stress. ..
  6. Yuan J, Lugea A, Zheng L, Gukovsky I, Edderkaoui M, Rozengurt E, et al. Protein kinase D1 mediates NF-kappaB activation induced by cholecystokinin and cholinergic signaling in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol. 2008;295:G1190-201 pubmed publisher
    ..Our results identify PKD1 as a novel early convergent point for PKCdelta and epsilon in the signaling pathways mediating NF-kappaB activation in pancreatitis. ..
  7. Hermanto U, Zong C, Li W, Wang L. RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002;22:2345-65 pubmed
  8. Serra R, Fang M, Park S, Hutchinson L, Green M. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. elife. 2014;3:e02313 pubmed publisher
    ..Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells. DOI:
  9. Pauken C, Capco D. The expression and stage-specific localization of protein kinase C isotypes during mouse preimplantation development. Dev Biol. 2000;223:411-21 pubmed
    ..Two isotypes have a stage-dependent nuclear localization. In addition, within each blastomere PKC isotypes occupy different subcellular locations in a stage-dependent fashion. ..
  10. Jensen E, Gopalakrishnan R, Westendorf J. Bone morphogenic protein 2 activates protein kinase D to regulate histone deacetylase 7 localization and repression of Runx2. J Biol Chem. 2009;284:2225-34 pubmed publisher
    ..These results establish a novel pathway by which BMP signaling regulates Runx2 activity via PKD-dependent inhibition of HDAC7 transcriptional repression. ..
  11. Krueger D, Osterweil E, Bear M. Activation of mGluR5 induces rapid and long-lasting protein kinase D phosphorylation in hippocampal neurons. J Mol Neurosci. 2010;42:1-8 pubmed publisher
    ..These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity. ..
  12. Chen Y, Chen Y, Huang S, Wang S. Protein kinase C? mediates adenosine-stimulated steroidogenesis in primary rat adrenal cells. FEBS Lett. 2010;584:4442-8 pubmed publisher
    ..Finally, inhibition of either A(2A)AR or A(2B)AR led to the suppression of PKC? phosphorylation. Together, these findings suggest that A(2)AR-PKC?-MEK signaling mediates Ado-stimulated adrenal steroidogenesis. ..
  13. Dirkx E, Cazorla O, Schwenk R, Lorenzen Schmidt I, Sadayappan S, Van Lint J, et al. Protein kinase D increases maximal Ca2+-activated tension of cardiomyocyte contraction by phosphorylation of cMyBP-C-Ser315. Am J Physiol Heart Circ Physiol. 2012;303:H323-31 pubmed publisher
    ..Thus, during high contraction frequency, PKD facilitates contraction of cardiomyocytes by increasing Ca(2+) sensitivity and by an increased T(max) through phosphorylation of cMyBP-C. ..
  14. Stathopoulou K, Cuello F, Candasamy A, Kemp E, Ehler E, Haworth R, et al. Four-and-a-half LIM domains proteins are novel regulators of the protein kinase D pathway in cardiac myocytes. Biochem J. 2014;457:451-61 pubmed publisher
  15. Song J, Li J, Qiao J, Jain S, Mark Evers B, Chung D. PKD prevents H2O2-induced apoptosis via NF-kappaB and p38 MAPK in RIE-1 cells. Biochem Biophys Res Commun. 2009;378:610-4 pubmed publisher
    ..Our findings suggest that PKD protects intestinal cells through up-regulation of NF-kappaB and down-regulation of p38 MAPK. ..
  16. Kim M, Wang F, Puthanveetil P, Kewalramani G, Innis S, Marzban L, et al. Cleavage of protein kinase D after acute hypoinsulinemia prevents excessive lipoprotein lipase-mediated cardiac triglyceride accumulation. Diabetes. 2009;58:2464-75 pubmed publisher
    ..CONCLUSIONS After severe hypoinsulinemia, activation of caspase-3 can restrict LPL translocation to the vascular lumen. When caspase-3 is inhibited, this compensatory response is lost, leading to lipid accumulation in the heart. ..
  17. Najibi M, Labed S, Visvikis O, IRAZOQUI J. An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense. Cell Rep. 2016;15:1728-42 pubmed publisher
    ..In addition, PKC? was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution. ..
  18. Sánchez Ruiloba L, Aicart Ramos C, Garcia Guerra L, Pose Utrilla J, Rodríguez Crespo I, Iglesias T. Protein kinase D interacts with neuronal nitric oxide synthase and phosphorylates the activatory residue serine 1412. PLoS ONE. 2014;9:e95191 pubmed publisher
  19. Tan M, Xu X, Ohba M, Ogawa W, Cui M. Thrombin rapidly induces protein kinase D phosphorylation, and protein kinase C delta mediates the activation. J Biol Chem. 2003;278:2824-8 pubmed
    ..Taken together, the findings of the present study demonstrate that thrombin induces activation of PKD and reveal a novel role of PKC delta in mediating thrombin-induced PKD activation in vascular smooth muscle cells. ..
  20. Ozgen N, Obreztchikova M, Guo J, Elouardighi H, Dorn G, Wilson B, et al. Protein kinase D links Gq-coupled receptors to cAMP response element-binding protein (CREB)-Ser133 phosphorylation in the heart. J Biol Chem. 2008;283:17009-19 pubmed publisher
  21. Storz P, Hausser A, Link G, Dedio J, Ghebrehiwet B, Pfizenmaier K, et al. Protein kinase C [micro] is regulated by the multifunctional chaperon protein p32. J Biol Chem. 2000;275:24601-7 pubmed
    ..Together, these findings identify p32 as a novel, compartment-specific regulator of PKC mu kinase activity. ..
  22. Wang J, Sinnett Smith J, Stevens J, Young S, Rozengurt E. Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells: A NOVEL ROLE FOR PROTEIN KINASE D (PKD). J Biol Chem. 2016;291:17988-8005 pubmed publisher
    ..The discovery of interaction between YAP and PKD pathways identifies a novel cross-talk in signal transduction and demonstrates, for the first time, that the PKDs feed into the YAP pathway. ..
  23. Bradford M, Soltoff S. P2X7 receptors activate protein kinase D and p42/p44 mitogen-activated protein kinase (MAPK) downstream of protein kinase C. Biochem J. 2002;366:745-55 pubmed
  24. Maturana A, Walchli S, Iwata M, Ryser S, Van Lint J, Hoshijima M, et al. Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel. Cardiovasc Res. 2008;78:458-65 pubmed publisher
    ..We propose a model where ENH1 scaffolds PKD1 to alpha1C in order to form a signalling complex that regulates the activity of cardiac L-type voltage-gated Ca(2+) channels. ..
  25. Rey O, Zhukova E, Sinnett Smith J, Rozengurt E. Vasopressin-induced intracellular redistribution of protein kinase D in intestinal epithelial cells. J Cell Physiol. 2003;196:483-92 pubmed
    ..These findings provide evidence for a mechanism by which PKC coordinates in intestinal epithelial cells the translocation and activation of PKD in response to vasopressin-induced GPCR activation. ..
  26. Cobbaut M, Derua R, Döppler H, Lou H, Vandoninck S, Storz P, et al. Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop. Sci Rep. 2017;7:887 pubmed publisher
  27. Edwards M, Johnson J, Rankin K, Jenkins R, Maguire C, Morgan A, et al. PKC-2 phosphorylation of UNC-18 Ser322 in AFD neurons regulates temperature dependency of locomotion. J Neurosci. 2012;32:7042-51 pubmed publisher
    ..These data demonstrate that an individual DAG-dependent thermosensory behavior of an organism is effected specifically by the downstream PKC-2 phosphorylation of UNC-18 on Ser322 in AFD neurons. ..
  28. Dirkx E, Schwenk R, Coumans W, Hoebers N, Angin Y, Viollet B, et al. Protein kinase D1 is essential for contraction-induced glucose uptake but is not involved in fatty acid uptake into cardiomyocytes. J Biol Chem. 2012;287:5871-81 pubmed publisher
    ..In conclusion, we present a novel contraction-induced ROS-DAPK-PKD1 pathway in cardiomyocytes. This pathway is activated separately from AMPK and mediates GLUT4 translocation/glucose uptake, but not CD36 translocation/LCFA uptake. ..
  29. Wang Y, Kedei N, Wang M, Wang Q, Huppler A, Toth A, et al. Interaction between protein kinase Cmu and the vanilloid receptor type 1. J Biol Chem. 2004;279:53674-82 pubmed
    ..6) Mutation of S116A in rVR1 blocked both the phosphorylation of rVR1 by PKCmu and the enhancement by PKCmu of the rVR1 response to capsaicin. We conclude that PKCmu functions as a direct modulator of rVR1. ..
  30. Jhun B, O Uchi J, Wang W, Ha C, Zhao J, Kim J, et al. Adrenergic signaling controls RGK-dependent trafficking of cardiac voltage-gated L-type Ca2+ channels through PKD1. Circ Res. 2012;110:59-70 pubmed publisher
    ..Our results uncover a novel molecular regulatory mechanism of VLCC trafficking and function in the heart and provide the first demonstration of physiological regulation of RGK function. ..
  31. Goodall M, Wardlow R, Goldblum R, Ziman A, Lederer W, Randall W, et al. Novel function of cardiac protein kinase D1 as a dynamic regulator of Ca2+ sensitivity of contraction. J Biol Chem. 2010;285:41686-700 pubmed publisher
    ..Taken together, these data reveal that localized PKD may play a role as a dynamic regulator of Ca(2+) sensitivity of contraction in cardiac myocytes. ..
  32. Sin Y, Baillie G. Heat shock protein 20 (HSP20) is a novel substrate for protein kinase D1 (PKD1). Cell Biochem Funct. 2015;33:421-6 pubmed publisher
    ..Our results suggest that both PKA and PKD1 can both phosphorylate HSP20 on serine 16 but that PKA is the most dominant. ..
  33. Tinsley J, Teasdale N, Yuan S. Involvement of PKCdelta and PKD in pulmonary microvascular endothelial cell hyperpermeability. Am J Physiol Cell Physiol. 2004;286:C105-11 pubmed
  34. Liljedahl M, Maeda Y, Colanzi A, Ayala I, van Lint J, Malhotra V. Protein kinase D regulates the fission of cell surface destined transport carriers from the trans-Golgi network. Cell. 2001;104:409-20 pubmed
    ..Our results suggest that PKD regulates the fission from the TGN of transport carriers that are en route to the cell surface. ..
  35. Sinnett Smith J, Ni Y, Wang J, Ming M, Young S, Rozengurt E. Protein kinase D1 mediates class IIa histone deacetylase phosphorylation and nuclear extrusion in intestinal epithelial cells: role in mitogenic signaling. Am J Physiol Cell Physiol. 2014;306:C961-71 pubmed publisher
    ..Collectively, our results reveal a PKD1-class IIa HDAC axis in intestinal epithelial cells leading to mitogenic signaling. ..
  36. Haworth R, Cuello F, Avkiran M. Regulation by phosphodiesterase isoforms of protein kinase A-mediated attenuation of myocardial protein kinase D activation. Basic Res Cardiol. 2011;106:51-63 pubmed publisher
    ..Furthermore, PDE3 and PDE4 play redundant roles in this process, such that inhibition of both isoforms is required to achieve PKA-mediated attenuation of PKD activation. ..
  37. Evans I, Bagherzadeh A, Charles M, Raynham T, Ireson C, Boakes A, et al. Characterization of the biological effects of a novel protein kinase D inhibitor in endothelial cells. Biochem J. 2010;429:565-72 pubmed publisher
    ..CRT5, a novel specific PKD inhibitor, will greatly facilitate the study of the role of PKD signalling mechanisms in angiogenesis. ..
  38. Jadali A, Ghazizadeh S. Protein kinase D is implicated in the reversible commitment to differentiation in primary cultures of mouse keratinocytes. J Biol Chem. 2010;285:23387-97 pubmed publisher