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FLASH GENE
Symbol PRKD2 contributors: mct - updated : 02-06-2015
HGNC name protein kinase D2
HGNC id 17293
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunespleen   highly
 thymus   highly
 tonsils   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • kinase domain
  • tyrosine kinase catalytic domain
  • a pleckstrin homology (PH) domain
  • C-terminal regulatory domain comprises two cysteine-rich domains (C1a/C1b), and PDZ-binding motifs that can target the kinases to distinct subcellular scaffolds through interactions with PDZ domain-containing proteins
    • HOMOLOGY
    Homologene
    FAMILY
  • Ser/Thr protein kinase family
  • PKD subfamily
    • CATEGORY receptor membrane G tyrosine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • phorbolester and growth factor stimulated protein kinase
  • implicated in the regulation of constitutive secretion in epithelial cells
  • controls the release of secretory granules in neuroendocrine tumour cells at the level of the Golgi apparatus
  • having a role in the proliferation and invasion of carcinoid tumors
  • having a role in controlling phorbol ester binding, catalytic activity, and nucleocytoplasmic shuttling
  • plays a role in numerous processes including cell proliferation, cell survival, immune cell signaling, gene expression, vesicle trafficking, and neuronal development
  • unlike PRKD1, PRKD2 catalytic activity is dispensable for normal embryogenesis
  • PRKD2 catalytic activity is, however, required for efficient antigen receptor-induced cytokine production in T-lymphocytes and for optimal T-cell-dependent antibody responses
  • a key role for PRKD2 in regulating the function of mature peripheral lymphocytes during adaptive immune responses
  • key signaling enzyme that mediate a range of physiologically important cellular responses
  • is a common signaling target downstream of various agonist receptors in platelets and G(q)-mediated signals along with calcium and novel PKC isoforms, in particular, PRKCD activate PRKD2 in platelets
  • novel role of RPKD1, PRKD2 as a regulator of RHOA activity and actin stress fiber formation through phosphorylation of rhotekin
  • has a restricted but critical role in T-cell antigen receptor signalling in mature T-cells
  • is involved in the regulation of PP2A activity in activated T cells through phosphorylation of Ser171 of SET
  • PRKD2 is a mediator of BCR-ABL transformation in chronic myelogenous leukemia
  • is essential for hypoxia-induced accumulation of HIF1A and activation of NFKB1 in tumor cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral membrane protein exit from TGN
  • interaction between PRKD2 and LCK (LCK regulated the activity of PRKD2 by tyrosine phosphorylation, which in turn may have modulated the physiological functions of PKD2 during TCR-induced T cell activation)
  • expression and kinase activity of PRKD2 are required for the ligand-inducible stimulation of IFNAR1 ubiquitination and endocytosis and for accelerated proteolytic turnover of IFNAR1
  • phosphorylation of rhotekin by PRKD2 modulates the anchoring of the RHOA in the plasma membrane
  • GTP-RAB5C bound to ASAP1, and activation of RAB5C by EGFR signaling was necessary to promote the intracellular association of ASAP1 and PRKD2
  • is a functionally significant mediator of the effect of GABPA, GABPB1, GABPB2 on proliferation and apoptosis of BCR-ABL–expressing cells
  • PRKD2, mediated BCL6B gene expression by VEGFA stimulation
  • CIB1A is a novel mediator of PRKD2-driven carcinogenesis and a potentially interesting therapeutic target in cancer
  • MMP9 enhances PRKD2-mediated tumor angiogenesis by releasing extracellular matrix-bound VEGFA, increasing its bioavailability and angiogenesis
  • PRKD2 promotes glioma cell proliferation by regulating GOLPH3 and then AKT activation
  • HSP90 binds to and stabilizes PRKD2 in human cancer cells
    • cell & other
    REGULATION
    activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells
    activated in an agonist-specific manner in cardiomyocytes
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    leads to increased proliferation and invasion of BON endocrine cells
    tumoral     --over  
    in pancreatic cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    pharmacologic inhibition of PRKD2 may represent a valuable approach to targeting the leukemic stem cell (LSC) in CML
    cancerbrainglioma/neuroblstoma
    PRKD2-GOLPH3-AKT signaling pathway might be a potential glioma therapeutic target
    ANIMAL & CELL MODELS