PRKD2
PRKD2 (Serine/threonine-protein kinase D2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
Overview
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) signalling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signalling 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) signalling, 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 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B.
IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Plasma Cell Myeloma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PRKD2 (Serine/threonine-protein kinase D2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
- 1 · What it is
PRKD2 (Serine/threonine-protein kinase D2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Multiple myeloma.
- 2 · What goes wrong in cancer
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) signalling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signalling 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.
- 3 · How drugs use it
No product in this corpus aims at PRKD2 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:17293 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q9BZL6 (protein name, function text, keywords and locations (REST API)); IntOGen PRKD2 (driver in 1 cohort (Act 1, LoF 0); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
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) signalling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signalling 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) signalling, 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 and Tyr-717 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. Location: Cytoplasm; Cell membrane; Nucleus; Golgi apparatus, trans-Golgi network (UniProt). Locus 19q13.32 (HGNC).
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"PRKD2" OR ABSTRACT:"PRKD2" OR TITLE:"protein kinase D2" OR ABSTRACT:"protein kinase D2" OR TITLE:"Serine/threonine-protein kinase D2" OR ABSTRACT:"Serine/threonine-protein kinase D2" OR TITLE:"PKD2" OR ABSTRACT:"PKD2" OR TITLE:"HSPC187" OR ABSTRACT:"HSPC187" OR TITLE:"DKFZP586E0820" OR ABSTRACT:"DKFZP586E0820") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PRKD2, not a curated reading list.