Download Gene Section PKD1 (protein kinase D1) Atlas of Genetics and Cytogenetics

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PKD1 (protein kinase D1)
Cheng Du, Meena Jaggi, Wenguang Zhang, KC Balaji
Urological Oncology Research, Urological Surgery, 982360, University of Nebraska Medical Center,
Omaha, NE 68198-2360, USA
Published in Atlas Database: January 2006
Online updated version: http://AtlasGeneticsOncology.org/Genes/PRKCMID41860ch14q11.html
DOI: 10.4267/2042/38316
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2006 Atlas of Genetics and Cytogenetics in Oncology and Haematology
homology (PH) and kinase domain (KD). Several
domain specific protein interactions and functions have
been described (see figure below).
Identity
Hugo: PRKD1
Other names: PKCmu; PRKCM
Location: 14q11
Localisation
DNA/RNA
In rested cells, the majority of PKD1 are in the
cytoplasm. When activated by phorbol ester, PKD1
rapidly moves to plasma membrane and nucleus.
Description
Function
The gene spans over 351 kb and the transcript consists
of 18 exons.
Serine/threonine kinase; protein kinase C downstream
effector; intracellular trafficking.
PKD1 has been shown to play a role in proliferation of
keratinocytes in skin, B and T lymphocytes and mast
cells signaling, possible role in development of central
tolerance in thymus gland, proliferation of pancreatic
cancer cells, cardiac myocyte contraction, endothelial
cell proliferation, osteoblasts differentiation, and
prostate cancer cells adhesion and invasion.
Transcription
About 3.8 kb in length; Expressed in several organs
with highest expression in kidney, heart and lungs.
Protein
Description
Homology
912 amino acids residues, 120 kDa on SDS-PAGE gel;
contains an alanine and proline rich (AP), two cysteinerich domains (CysI and CysII), acidic (AC), pleckstrin
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3)
Homologues present in mouse and rat.
159
PKD1 (protein kinase D1)
Du C et al.
Implicated in
kinase C-dependent signal transduction pathway. EMBO J
1996 Nov 15;15(22):6220-6230.
Advanced prostate cancer
Bowden ET, Barth M, Thomas D, Glazer RI, Mueller SC. An
invasion-related complex of cortactin, paxillin and PKCmu
associates with invadopodia at sites of extracellular matrix
degradation. Oncogene 1999;18(31):4440-4449.
Disease
PKD1 phosphorylates E-cadherin in prostate cancer
cell lines. E-cadherin phosphorylation is associated
with altered cellular aggregation and motility in
prostate cancer. Inhibition of PKD1 activity by the
selective inhibitor Go6976 in LNCaP cells resulted in
decreased cellular aggregation and over expression of
PKD1 in C4-2 prostate cancer cells increased cellular
aggregation and decreased cellular motility.
Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A,
Pfizenmaier K, Johannes FJ. Protein kinase C mu is negatively
regulated by 14-3-3 signal transduction proteins. J Biol Chem
1999;274(14):9258-9264.
Waldron RT, Iglesias T, Rozengurt E. Phosphorylationdependent protein kinase D activation. Electrophoresis
1999;20(2):382-390. (Review).
Matthews SA, Rozengurt E, Cantrell D. Protein kinase D. A
selective target for antigen receptors and a downstream target
for protein kinase C in lymphocytes. J Exp Med
2000;191(12):2075-2082.
Cardiac hypertrophy
Disease
Transcriptional regulation of gene expression is tightly
coupled to histone deacetylases (HDAC) and histone
acetyltransferase (HAT) that modify the access of
transcription factors to DNA binding sites. PKD1 has
been shown to participate in nuclear export of HDAC5.
HDAC5 is phosphorylated by PKD1 in cardiac
myocytes, which results in the binding of 14-3-3
protein to the phosphoserine motif on HDAC5, thus
leading to nuclear export through a CRM1-dependent
mechanism. This results in increased transcriptional
activity of hypertrophy mediating genes in myocytes.
Cardiac failure is usually preceded by cardiac
hypertrophy that is mediated by altered gene expression
involved in myocyte contraction, calcium handling and
metabolism. PKD1 specific inhibitors may be of benefit
in limiting cardiac hypertrophy.
Vertommen D, Rider M, Ni Y, Waelkens E, Merlevede W,
Vandenheede JR, Van Lint J. Regulation of protein kinase D
by multisite phosphorylation. Identification of phosphorylation
sites by mass spectrometry and characterization by sitedirected mutagenesis. J Biol Chem 2000;275(26):1956719576.
Rey O, Sinnett-Smith J, Zhukova E, Rozengurt E. Regulated
nucleocytoplasmic transport of protein kinase D in response to
G protein-coupled receptor activation. J Biol Chem
2001;276(52):49228-49235.
Waldron RT, Rey O, Iglesias T, Tugal T, Cantrell D, Rozengurt
E. Activation loop Ser744 and Ser748 in protein kinase D are
transphosphorylated in vivo. J Biol Chem 2001;276(35):3260632615.
Hausser A, Link G, Bamberg L, Burzlaff A, Lutz S, Pfizenmaier
K, Johannes FJ. Structural requirements for localization and
activation of protein kinase C mu (PKC mu) at the Golgi
compartment. J Cell Biol 2002;156(1):65-74.
Lint JV, Rykx A, Vantus T, Vandenheede JR. Getting to know
protein kinase D. Int J Biochem Cell Biol 2002;34(6):577-581.
(Review).
References
Rykx A, De Kimpe L, Mikhalap S, Vantus T, Seufferlein T,
Vandenheede JR, Van Lint J. Protein kinase D: a family affair.
FEBS Lett 2003;546(1):81-86. (Review).
Johannes FJ, Prestle J, Eis S, Oberhagemann P, Pfizenmaier
K. PKCu is a novel, atypical member of the protein kinase C
family. J Biol Chem 1994;269(8):6140-6148.
Waldron RT, Rozengurt E. Protein kinase C phosphorylates
protein kinase D activation loop Ser744 and Ser748 and
releases autoinhibition by the pleckstrin homology domain. J
Biol Chem 2003;278(1):154-163.
Valverde AM, Sinnett-Smith J, Van Lint J, Rozengurt E.
Molecular cloning and characterization of protein kinase D: a
target for diacylglycerol and phorbol esters with a distinctive
catalytic domain. Proc Natl Acad Sci USA 1994;91(18):85728576.
Jaggi M, Rao PS, Smith DJ, Wheelock MJ, Johnson KR,
Hemstreet GP, Balaji KC. E-cadherin phosphorylation by
protein kinase D1/protein kinase C{mu} is associated with
altered cellular aggregation and motility in prostate cancer.
Cancer Res 2005;65(2):483-492.
Van Lint JV, Sinnett-Smith J, Rozengurt E. Expression and
characterization of PKD, a phorbol ester and diacylglycerolstimulated
serine
protein
kinase.
J
Biol
Chem
1995;270(3):1455-1461.
Rozengurt E, Rey O, Waldron RT. Protein kinase D signaling.
J Biol Chem 2005;280(14):13205-13208. (Review).
Sidorenko SP, Law CL, Klaus SJ, Chandran KA, Takata M,
Kurosaki T, Clark EA. Protein kinase C mu (PKC mu)
associates with the B cell antigen receptor complex and
regulates lymphocyte signaling. Immunity 1996;5(4):353-363.
This article should be referenced as such:
Du C, Jaggi M, Zhang W, Balaji KC. PKD1 (protein kinase D1).
Atlas Genet Cytogenet Oncol Haematol.2006;10(3):159-160.
Zugaza JL, Sinnett-Smith J, Van Lint J, Rozengurt E. Protein
kinase D (PKD) activation in intact cells through a protein
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3)
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