2coa

Structural highlights

Function

[KPCD2_HUMAN] Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. In response to oxidative stress, is phosphorylated at Tyr-438 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B. In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77. Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation. During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens. In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway. During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane. Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis. In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Protein kinase C 3D structures

References

1. ↑ Mihailovic T, Marx M, Auer A, Van Lint J, Schmid M, Weber C, Seufferlein T. Protein kinase D2 mediates activation of nuclear factor kappaB by Bcr-Abl in Bcr-Abl+ human myeloid leukemia cells. Cancer Res. 2004 Dec 15;64(24):8939-44. PMID:15604256 doi:10.1158/0008-5472.CAN-04-0981
2. ↑ Yeaman C, Ayala MI, Wright JR, Bard F, Bossard C, Ang A, Maeda Y, Seufferlein T, Mellman I, Nelson WJ, Malhotra V. Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network. Nat Cell Biol. 2004 Feb;6(2):106-12. Epub 2004 Jan 25. PMID:14743217 doi:10.1038/ncb1090
3. ↑ Irie A, Harada K, Tsukamoto H, Kim JR, Araki N, Nishimura Y. Protein kinase D2 contributes to either IL-2 promoter regulation or induction of cell death upon TCR stimulation depending on its activity in Jurkat cells. Int Immunol. 2006 Dec;18(12):1737-47. Epub 2006 Oct 31. PMID:17077180 doi:10.1093/intimm/dxl108
4. ↑ Chiu TT, Leung WY, Moyer MP, Strieter RM, Rozengurt E. Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 production in nontransformed human colonic epithelial cells through NF-kappaB. Am J Physiol Cell Physiol. 2007 Feb;292(2):C767-77. Epub 2006 Aug 23. PMID:16928771 doi:10.1152/ajpcell.00308.2006
5. ↑ von Blume J, Knippschild U, Dequiedt F, Giamas G, Beck A, Auer A, Van Lint J, Adler G, Seufferlein T. Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2. EMBO J. 2007 Nov 14;26(22):4619-33. Epub 2007 Oct 25. PMID:17962809 doi:10.1038/sj.emboj.7601891
6. ↑ Ge X, Low B, Liang M, Fu J. Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation. J Pharmacol Sci. 2007 Oct;105(2):168-76. PMID:17951978
7. ↑ von Wichert G, Edenfeld T, von Blume J, Krisp H, Krndija D, Schmid H, Oswald F, Lother U, Walther P, Adler G, Seufferlein T. Protein kinase D2 regulates chromogranin A secretion in human BON neuroendocrine tumour cells. Cell Signal. 2008 May;20(5):925-34. doi: 10.1016/j.cellsig.2008.01.003. Epub 2008, Jan 16. PMID:18262756 doi:10.1016/j.cellsig.2008.01.003
8. ↑ Li Q, Sun X, Wu J, Lin Z, Luo Y. PKD2 interacts with Lck and regulates NFAT activity in T cells. BMB Rep. 2009 Jan 31;42(1):35-40. PMID:19192391
9. ↑ Hao Q, Wang L, Zhao ZJ, Tang H. Identification of protein kinase D2 as a pivotal regulator of endothelial cell proliferation, migration, and angiogenesis. J Biol Chem. 2009 Jan 9;284(2):799-806. doi: 10.1074/jbc.M807546200. Epub 2008, Nov 9. PMID:19001381 doi:10.1074/jbc.M807546200