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FLASH GENE
Symbol PAK4 contributors: mct/pgu - updated : 23-10-2016
HGNC name p21 protein (Cdc42/Rac)-activated kinase 4
HGNC id 16059
Location 19q13.2      Physical location : 39.616.419 - 39.670.046
Synonym name
  • protein kinase related to S. cerevisiae STE20, effector for Cdc42Hs
  • p21(CDKN1A)-activated kinase 4
    • Synonym symbol(s) KIAA1142, PAK-4
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 53.63 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 2838 - 591 - 1998 9822598
    11 - 3064 - 591 - 1998 9822598
    9 - 2765 - 591 - 1998 9822598
    8 - 2306 - 438 - 1998 9822598
    9 - 2379 - 438 - 1998 9822598
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Mus musculusFetal
    Reproductivefemale systembreast  lowly Homo sapiens
     male systemtestis  highly
     male systemprostate  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
     epithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal regulatory domain with a CDC42/RAC1 binding domain (CRIB)
  • a GTPase bi nding domain
  • a C terminal kinase region of serine/threonine kinases
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to Drosophila Mbt
    homolog to C.elegans C45b11.1
    intraspecies homolog to PAK6
    Homologene
    FAMILY
  • protein kinase superfamily
  • STE Ser/Thr protein kinase family
  • STE20 subfamily
    • CATEGORY enzyme , receptor membrane serine/threonine kinase
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    text
  • colocalized with polymerized actin clusters and with beta coat protein
  • in response to HGF, Gab1 and Pak4 associate and colocalize at the cell periphery within lamellipodia
    • basic FUNCTION
  • cell shape and cell size control
  • linking Rho GTPases to cytoskeleton reorganisation and nuclear signaling
  • playing a role in pancreas ductal adenocarcinoma cellular migration and invasion
  • mediator of filopodia formation, playing a role in the reorganisation of the actin cytoskeleton (suggesting a role for the Golgi in cell morphogenesis)
  • playing a role in the regulation of cytoskeletal organization and cell and/or extracellular matrix adhesion, and in neural tube development
  • in response to HGF, Gab1 and Pak4 synergize to enhance epithelial cell dispersal, migration and invasion
  • key integrator of cell migration and invasive growth downstream from the Met receptor
  • functions in TNF-alpha-induced survival pathways by facilitating TRADD binding to the TNF receptor
  • mediates morphological changes through the regulation of GEF-H1
  • can negatively regulate the activation of Rho through a direct protein-protein interaction with G protein-linked Rho GEFs
  • determine podosome size and number in macrophages through localized actin regulation
  • increases cell migration speed in synergy with LIMK1 in prostate
  • disrupts mammary acinar architecture and promotes mammary tumorigenesiscancer cells
  • regulates cytoskeletal organization, and controls cell growth, proliferation, and survival
  • may play a critical role in the regulation of neural progenitor cell proliferation and in establishing the foundation for development of the adult brain
  • regulates cytoskeletal architecture, and controls cell proliferation and survival
  • required for regulation of the cell-cycle regulatory protein CDKN1A, and for control of cell-cycle progression
  • critical molecule coordinating cytoskeletal systems for efficient cell migration
  • regulates regulatory myosin light chain phosphorylation and myosin contractility during FCGR-mediated phagocytosis
  • PAK4 functions, including control of actin dynamics, are necessary for normal development of the heart
  • involved in the regulation of the G1 phase and the G2/M transition of the cell cycle
  • has a key role in the oncogenic transformation of breast cells
  • is an important regulator of endometrial cancer cell migration and invasion
    • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    PHYSIOLOGICAL PROCESS
    text
  • cell structure
    • PATHWAY
    metabolism
    signaling signal transduction
    JNK pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GTP bound CDC42Hs (specifically)
  • RAC1 (weakly)
  • activating weakly the JNK family of MAP kinases (JNK
    • pathway)
  • interacting with FGFR2 (KGFR) and mediating antiapoptotic effects of FGF7 (KGF) on epithelial cells
  • Gab1-interacting protein
  • PAK4 contributes to FCGR-mediated uptake downstream of actin cup formation by regulating phosphorylation of myosin regulatory light chain
  • PAK4 kinase activity and associated LIMK1 activity are essential for carcinoma cell motility, highlighting PAK4 as a potential anti-metastatic therapeutic target
  • physical association between PAK4 and MM2, suggesting the future therapeutic potential of PAK4/MMP2 dual targeting in glioma treatment
  • SH3RF2 regulates PAK4 protein stability (SH3RF2 inhibits PAK4 ubiquitination via physical interaction-mediated steric hindrance, which results in the upregulation of PAK4 protein)
  • CCM2 and PAK4 are important downstream mediators of NPPA/NPR1 signaling involved in cell spreading, an important initial step in the enhancement of endothelial barrier function
  • PAK4 promoted glucose intake, NADPH production and lipid bisynthesis, leading to an increased proliferation of colon cancer cells
  • mechanistically, PAK4 interacted with G6PD, a rate-limiting enzyme of the pentose phosphate pathway and increased G6PD activity via enhancing MDM2-mediated TP53 ubiquitination degradation
    • cell & other
    REGULATION
    activated by Rho family GTPases (CDC42 and RAC1)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --over  
    in pancreas ductal adenocarcinoma
    tumoral     --over  
    triggers events that are important for the transformation of mammary epithelial cells (
    tumoral     --over  
    in multiple human endometrial cancer (EC) cell lines
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    blocking PAK4-mediated STMN2 phosphorylation might be a potential therapeutic strategy for metastasis of gastric cancer
    cancerreproductiveuterus
    may be a promising target for the treatment of metastatic endometrial cancer (EC)
    cancerdigestivecolon
    PAK4 and/or G6PD blockage might be a potential therapeutic strategy for colon cancer
    ANIMAL & CELL MODELS