PKD1 (Protein Kinase D1)

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PKD1 (Protein Kinase D1)

Identity

Other names PKCmu

PRKCM

HGNC PRKD1

Location 14q11

Location_base_pair Starts at 29115438 and ends at 29466650 bp from pter ( according to hg18-Mar_2006).

DNA/RNA

Description The gene spans over 351 kb and the transcript consists of 18 exons

Transcription About 3.8 kb in length; Expressed in several organs with highest expression in kidney, heart and lungs.

Protein

Description 912 amino acids residues, 120 kDa on SDS-PAGE gel; contains an alanine and proline rich (AP), two cysteine-rich domains (CysI and CysII), acidic (AC), pleckstrin homology (PH) and kinase domain (KD). Several domain specific protein interactions and functions have been described (see figure below).

Localisation In rested cells, the majority of PKD1 are in the cytoplasm. When activated by phorbol ester, PKD1 rapidly moves to plasma membrane and nucleus.

Function 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.

Homology Homologues present in mouse and rat.

Implicated in

Entity Advanced prostate cancer

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.

Entity 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.

External links

	Nomenclature
HGNC	PRKD1 9407
Entrez_Gene	PRKD1 5587 protein kinase D1
	Cards
Atlas	PRKCMID41860ch14q11
GeneCards	PRKD1
Ensembl	ENSG00000184304 [Gene_View] PRKD1 [Vega]
Genatlas	PRKD1
	Genomic and cartography
GoldenPath	PRKD1 - 14q11 chr14:29115438-29466650 - 14q11 [Description] (hg18-Mar_2006)
Ensembl	PRKD1 - 14q11 [CytoView]
NCBI	Mapview
OMIM	605435 Disease map [OMIM]
HomoloGene	PRKD1
	Gene and transcription
Genbank	AK314170 [ ENTREZ ]
Genbank	BC160015 [ ENTREZ ]
Genbank	BX645735 [ ENTREZ ]
Genbank	CN412379 [ ENTREZ ]
Genbank	X75756 [ ENTREZ ]
RefSeq	NM_002742 [ SRS ] NM_002742 [ ENTREZ ]
RefSeq	AC_000057 [ SRS ] AC_000057 [ ENTREZ ]
RefSeq	AC_000146 [ SRS ] AC_000146 [ ENTREZ ]
RefSeq	NC_000014 [ SRS ] NC_000014 [ ENTREZ ]
RefSeq	NT_026437 [ SRS ] NT_026437 [ ENTREZ ]
RefSeq	NW_001838110 [ SRS ] NW_001838110 [ ENTREZ ]
RefSeq	NW_925539 [ SRS ] NW_925539 [ ENTREZ ]
CCDS	PRKD1 CCDS - NCBI
AceView	PRKD1 AceView - NCBI
Unigene	Hs.508999 [ SRS ] Hs.508999 [ NCBI ]
Fast-db	126 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q15139 [ SRS] Q15139 [ EXPASY ] Q15139 [ INTERPRO ] Q15139 [ UNIPROT ] Q15139 [ VarSplice FASTA ]
Prosite	PS50003 PH_DOMAIN [ SRS ] PS50003 PH_DOMAIN [ Expasy ]
Prosite	PS00107 PROTEIN_KINASE_ATP [ SRS ] PS00107 PROTEIN_KINASE_ATP [ Expasy ]
Prosite	PS50011 PROTEIN_KINASE_DOM [ SRS ] PS50011 PROTEIN_KINASE_DOM [ Expasy ]
Prosite	PS00108 PROTEIN_KINASE_ST [ SRS ] PS00108 PROTEIN_KINASE_ST [ Expasy ]
Prosite	PS00479 ZF_DAG_PE_1 [ SRS ] PS00479 ZF_DAG_PE_1 [ Expasy ]
Prosite	PS50081 ZF_DAG_PE_2 [ SRS ] PS50081 ZF_DAG_PE_2 [ Expasy ]
Interpro	IPR002219 DAG_PE_bd [ SRS ] IPR002219 DAG_PE_bd [ EBI ]
Interpro	IPR001849 PH [ SRS ] IPR001849 PH [ EBI ]
Interpro	IPR011993 PH_type [ SRS ] IPR011993 PH_type [ EBI ]
Interpro	IPR015727 PKC_mu_like [ SRS ] IPR015727 PKC_mu_like [ EBI ]
Interpro	IPR000719 Prot_kinase_core [ SRS ] IPR000719 Prot_kinase_core [ EBI ]
Interpro	IPR017441 Protein_kinase_ATP_bd_CS [ SRS ] IPR017441 Protein_kinase_ATP_bd_CS [ EBI ]
Interpro	IPR017442 Se/Thr_pkinase-rel [ SRS ] IPR017442 Se/Thr_pkinase-rel [ EBI ]
Interpro	IPR008271 Ser_thr_pkin_AS [ SRS ] IPR008271 Ser_thr_pkin_AS [ EBI ]
Interpro	IPR002290 Ser_thr_pkinase [ SRS ] IPR002290 Ser_thr_pkinase [ EBI ]
CluSTr	Q15139
Pfam	PF00130 C1_1 [ SRS ] PF00130 C1_1 [ Sanger ] pfam00130 [ NCBI-CDD ]
Pfam	PF00169 PH [ SRS ] PF00169 PH [ Sanger ] pfam00169 [ NCBI-CDD ]
Pfam	PF00069 Pkinase [ SRS ] PF00069 Pkinase [ Sanger ] pfam00069 [ NCBI-CDD ]
Smart	SM00109 C1 [EMBL]
Smart	SM00233 PH [EMBL]
Smart	SM00220 S_TKc [EMBL]
Prodom	PD000001 Prot_kinase[INRA-Toulouse]
Prodom	Q15139 KPCD1_HUMAN [ Domain structure ] Q15139 KPCD1_HUMAN [ sequences sharing at least 1 domain ]
Blocks	Q15139
HPRD	05668
	Protein Interaction databases
DIP	Q15139
IntAct	Q15139
	Polymorphism : SNP, mutations, diseases
OMIM	605435 [ map ]
GENETests	605435
SNP	PRKD1 [dbSNP-NCBI]
SNP	NM_002742 [SNP-NCI]
SNP	PRKD1 [GeneSNPs - Utah] PRKD1] [HGBASE - SRS]
HAPMAP	PRKD1 [HAPMAP]
COSMIC	PRKD1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	PRKD1
Genetic Association	PRKD1
CDC HuGE	PRKD1
	General knowledge
Family Browser	PRKD1 [UCSC Family Browser]
SOURCE	NM_002742
SMD	Hs.508999
SAGE	Hs.508999
Enzyme	2.7.11.13 [ Enzyme-Expasy ] 2.7.11.13 [ Enzyme-SRS ] 2.7.11.13 [ IntEnz-EBI ] 2.7.11.13 [ BRENDA ] 2.7.11.13 [ KEGG ]
GO	nucleotide binding [Amigo] nucleotide binding
GO	atypical protein kinase C activity [Amigo] atypical protein kinase C activity
GO	protein binding [Amigo] protein binding
GO	ATP binding [Amigo] ATP binding
GO	cytosol [Amigo] cytosol
GO	plasma membrane [Amigo] plasma membrane
GO	integral to plasma membrane [Amigo] integral to plasma membrane
GO	protein amino acid phosphorylation [Amigo] protein amino acid phosphorylation
GO	intracellular signaling cascade [Amigo] intracellular signaling cascade
GO	zinc ion binding [Amigo] zinc ion binding
GO	cell proliferation [Amigo] cell proliferation
GO	transferase activity [Amigo] transferase activity
GO	diacylglycerol binding [Amigo] diacylglycerol binding
GO	metal ion binding [Amigo] metal ion binding
PubGene	PRKD1
TreeFam	PRKD1
CTD	5587 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PRKD1 Related clones (RZPD - Berlin)
	PubMed
PubMed	70 Pubmed reference(s) in Entrez

Bibliography

PKCu is a novel, atypical member of the protein kinase C family.

Johannes FJ, Prestle J, Eis S, Oberhagemann P, Pfizenmaier K

The Journal of biological chemistry. 1994 ; 269 (8) : 6140-6148.

PMID 8119958

Molecular cloning and characterization of protein kinase D: a target for diacylglycerol and phorbol esters with a distinctive catalytic domain.

Valverde AM, Sinnett-Smith J, Van Lint J, Rozengurt E

Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (18) : 8572-8576.

PMID 8078925

Expression and characterization of PKD, a phorbol ester and diacylglycerol-stimulated serine protein kinase.

Van Lint JV, Sinnett-Smith J, Rozengurt E

The Journal of biological chemistry. 1995 ; 270 (3) : 1455-1461.

PMID 7836415

Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex and regulates lymphocyte signaling.

Sidorenko SP, Law CL, Klaus SJ, Chandran KA, Takata M, Kurosaki T, Clark EA

Immunity. 1996 ; 5 (4) : 353-363.

PMID 8885868

Protein kinase D (PKD) activation in intact cells through a protein kinase C-dependent signal transduction pathway.

Zugaza JL, Sinnett-Smith J, Van Lint J, Rozengurt E

The EMBO journal. 1996 ; 15 (22) : 6220-6230.

PMID 8947045

An invasion-related complex of cortactin, paxillin and PKCmu associates with invadopodia at sites of extracellular matrix degradation.

Bowden ET, Barth M, Thomas D, Glazer RI, Mueller SC

Oncogene. 1999 ; 18 (31) : 4440-4449.

PMID 10442635

Protein kinase C mu is negatively regulated by 14-3-3 signal transduction proteins.

Hausser A, Storz P, Link G, Stoll H, Liu YC, Altman A, Pfizenmaier K, Johannes FJ

The Journal of biological chemistry. 1999 ; 274 (14) : 9258-9264.

PMID 10092600

Phosphorylation-dependent protein kinase D activation.

Waldron RT, Iglesias T, Rozengurt E

Electrophoresis. 1999 ; 20 (2) : 382-390.

PMID 10197446

Protein kinase D. A selective target for antigen receptors and a downstream target for protein kinase C in lymphocytes.

Matthews SA, Rozengurt E, Cantrell D

The Journal of experimental medicine. 2000 ; 191 (12) : 2075-2082.

PMID 10859332

Regulation of protein kinase D by multisite phosphorylation. Identification of phosphorylation sites by mass spectrometry and characterization by site-directed mutagenesis.

Vertommen D, Rider M, Ni Y, Waelkens E, Merlevede W, Vandenheede JR, Van Lint J

The Journal of biological chemistry. 2000 ; 275 (26) : 19567-19576.

PMID 10867018

Regulated nucleocytoplasmic transport of protein kinase D in response to G protein-coupled receptor activation.

Rey O, Sinnett-Smith J, Zhukova E, Rozengurt E

The Journal of biological chemistry. 2001 ; 276 (52) : 49228-49235.

PMID 11641411

Activation loop Ser744 and Ser748 in protein kinase D are transphosphorylated in vivo.

Waldron RT, Rey O, Iglesias T, Tugal T, Cantrell D, Rozengurt E

The Journal of biological chemistry. 2001 ; 276 (35) : 32606-32615.

PMID 11410586

Structural requirements for localization and activation of protein kinase C mu (PKC mu) at the Golgi compartment.

Hausser A, Link G, Bamberg L, Burzlaff A, Lutz S, Pfizenmaier K, Johannes FJ

The Journal of cell biology. 2002 ; 156 (1) : 65-74.

PMID 11777941

Getting to know protein kinase D.

Lint JV, Rykx A, Vantus T, Vandenheede JR

The international journal of biochemistry & cell biology. 2002 ; 34 (6) : 577-581.

PMID 11943587

Protein kinase D: a family affair.

Rykx A, De Kimpe L, Mikhalap S, Vantus T, Seufferlein T, Vandenheede JR, Van Lint J

FEBS letters. 2003 ; 546 (1) : 81-86.

PMID 12829240

Protein kinase C phosphorylates protein kinase D activation loop Ser744 and Ser748 and releases autoinhibition by the pleckstrin homology domain.

Waldron RT, Rozengurt E

The Journal of biological chemistry. 2003 ; 278 (1) : 154-163.

PMID 12407104

E-cadherin phosphorylation by protein kinase D1/protein kinase C{mu} is associated with altered cellular aggregation and motility in prostate cancer.

Jaggi M, Rao PS, Smith DJ, Wheelock MJ, Johnson KR, Hemstreet GP, Balaji KC

Cancer research. 2005 ; 65 (2) : 483-492.

PMID 15695390

Protein kinase D signaling.

Rozengurt E, Rey O, Waldron RT

The Journal of biological chemistry. 2005 ; 280 (14) : 13205-13208.

PMID 15701647

REVIEW articles automatic search in PubMed

Last year publications automatic search in PubMed

Search in all EBI NCBI

Contributor(s)

Written 01-2006 C Du, M Jaggi, W Zhang, KC Balaji

Division of Urology, University of Massachusetts Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01605, USA

Citation

This paper should be referenced as such :
Du C, Jaggi M, Zhang W, Balaji KC . PKD1 (Protein Kinase D1). Atlas Genet Cytogenet Oncol Haematol. January 2006 .
URL : http://AtlasGeneticsOncology.org/Genes/PRKCMID41860ch14q11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Nov 27 13:27:56 2008

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us
jlhuret@AtlasGeneticsOncology.org.

Other names	PKCmu
	PRKCM
HGNC	PRKD1
Location	14q11
Location_base_pair	Starts at 29115438 and ends at 29466650 bp from pter ( according to hg18-Mar_2006).

Description	The gene spans over 351 kb and the transcript consists of 18 exons
Transcription	About 3.8 kb in length; Expressed in several organs with highest expression in kidney, heart and lungs.



Description	912 amino acids residues, 120 kDa on SDS-PAGE gel; contains an alanine and proline rich (AP), two cysteine-rich domains (CysI and CysII), acidic (AC), pleckstrin homology (PH) and kinase domain (KD). Several domain specific protein interactions and functions have been described (see figure below).
Localisation	In rested cells, the majority of PKD1 are in the cytoplasm. When activated by phorbol ester, PKD1 rapidly moves to plasma membrane and nucleus.
Function	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.
Homology	Homologues present in mouse and rat.

Entity	Advanced prostate cancer
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.

Entity	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.

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Written	01-2006	C Du, M Jaggi, W Zhang, KC Balaji
		Division of Urology, University of Massachusetts Memorial Medical Center, 55 Lake Avenue North, Worcester, MA 01605, USA