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FLASH GENE
Symbol PTK2 contributors: shn/npt/pgu - updated : 14-02-2017
HGNC name PTK2 protein tyrosine kinase 2
HGNC id 9611
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal FERM domain arranges into three lobes and regulates its kinase activity, and including a nuclear export signal NES1, and implicated in events at the cell cortex and in the nucleus that are crucial to cell behaviour and life-or-death decisions
  • a protein kinase domain including a nuclear export signal NES2
  • a NT2 domain, overexpressed and co-localized with IGF1R in pancreatic cells
  • focal adhesion targeting (FAT) domain binds specifically to the CD4 endocytosis motif
  • C-terminal domain can bind to a number of proteins, such as paxillin, talin, phosphoinositide 3-kinases (PI3 K) and the GTPase-activating protein ARHGAP26, leading to the localization of FAK to focal adhesions and reorganization of the actin cytoskeleton
  • conjugated Other
    HOMOLOGY
    interspecies ortholog to Ptk2, Rattus norvegicus
    ortholog to Ptk2, Mus musculus
    ortholog to PTK2, Pan troglodytes
    homolog to zgc:66114, Danio rerio
    Homologene
    FAMILY
  • FAK subfamily of protein tyrosine kinases
  • CATEGORY adhesion , enzyme , immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,nucleolus
    text
  • localized to focal adhesions
  • lamellipodium
  • apical plasma membrane
  • nuclear translocation of PTK2 reduces contact between PTK2 and SRC
  • basic FUNCTION
  • non receptor, protein tyrosine kinase, focal adhesion kinase, playing an important role in the response of migrating cells to mechanical input
  • mediating a direct interaction with the C terminal SH2 domain of phospholipase C (PCLG1)
  • primary mediator of integrin signaling after integrin mediated cell adhesion and PTK2 phosphorylation
  • involved in cell mobility
  • playing a potential role in oncogenic transformations resulting in increased kinase activity
  • plays crucial role in a variety of intracellular signaling, such as migration, proliferation, differentiation, and adhesion
  • promotes cell migration by regulating focal adhesion formation and turnover through multiple signaling connections
  • playing a necessary role for cell migration and tube formation
  • may be a critical signaling component involved in the regulation of angiogenesis
  • is functioning in cell migration, but fibril-forming collagen-induced PTK2 degradation is necessary for endothelial tube formation
  • SRC and PTK2 cooperate to phosphorylate GIT2, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness
  • plays a critical role in transformation and tumorigenesis and is aberrantly upregulated in many types of cancer
  • central component in integrin signalling, and in T lymphocytes, with CD4 localise to the same signalling complexes after stimulation by either the human immunodeficiency virus (HIV) gp120 glycoprotein or an antigen
  • mediates activation-loop independent phosphorylation, as well as Akt and ERK activation
  • playing a role in phosphorylation, signaling and stability of the IGF1R
  • critical tyrosine kinase that modulates cell adhesion, migration, proliferation and survival in response to extracellular signals
  • EMP2-FAK association is a significant functional cellular responses in the context of in vitro models of proliferative vitreoretinopathy
  • acts as a pivotal signal 'integrator', controlling and coordinating cellular responses that include cell migration, survival, proliferation and, epithelial tissue repair after DNA damage
  • PTK2 and IQGAP1 regulate melusin-dependent cardiomyocyte hypertrophy and survival through MAPK1/MAPK3 activation
  • controls filopodia formation and actin nucleation during axonal development
  • regulates intestinal epithelial barrier function via redistribution of tight junction
  • involved in cell adhesion and, in neurons, and plays a role in axonal guidance, and neurite growth and attraction
  • distinct kinase-dependent and -independent activities of PTK2 differentially regulate luminal progenitors and basal mammary stem cells
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    cell organization/biogenesis
    cell migration & motility
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , development , immunity/defense , inflammation
    text
  • angiogenesis
  • central nervous system neuron axonogenesis
  • endothelial cell migration
  • microtubule cytoskeleton organization and biogenesis
  • neuron migration
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
  • PTK2/ELK1 complex is found, mainly, in the cytoplasm, near the nuclear membrane periphery, raising the possibility that ELK1 may have alternative extranuclear function
  • PTK2-CD4 complex represents an alternative route for eliciting T-cell-specific signals and it links gp120 engagement to distinctive T-cell signalling during HIV infection
  • part of PTK2-RASA1-GRLF1 complex that regulates polarity in migrating cells
  • within FAC (focal adhesion complex), the focal adhesion kinase (PTK2) and PTK2B are believed to act as important scaffolding proteins
  • ABCB1 and an integrated component of the occludin/zonula occludens 1 (TJP1) adhesion complex at the BTB, structurally interacted with PTK2, creating the OCLN/TJP1/PTK2/ABCB1 regulatory complex
  • PTK2 formed a complex with its E2 enzyme, UBE2H, and E3 enzyme, TRIM72
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • growth factor receptor-bound protein 2, GBR2
  • Crk-associated tyrosine kinase substrate p130Cas
  • talin 1, TLN1
  • Rho GTPase activating protein 26, ARHGAP26
  • neural precursor cell expressed, developmentally down-regulated 9, NEDD9
  • Syk protein-tyrosine kinase, Syk
  • protein tyrosine kinase 2 beta, PTK2B
  • transforming growth factor beta 1 induced transcript 1, TGFB1I1
  • c-Cbl-associated protein, CAP
  • Janus kinase 2, JAK2
  • insulin receptor substrate 1, IRS1
  • embryonal Fyn-associated substrate, Efs
  • growth factor receptor-bound protein 7, GBR7
  • phosphatase and tensin homolog, PTEN
  • PDGF- and EGF-receptor (PDGFR and EGFR) signalling complexes
  • EPH receptor A2, EPHA2
  • polycystic kidney disease 1, PKD1
  • transforming growth factor beta 1 induced transcript 1, TGFB1I1
  • interaction between the PH domain of Etk and the FERM domain of FAK
  • Ezrin, EZR
  • ArfGAP with SH3 domain, ankyrin repeat and PH domain 1, ASAP1
  • c-Jun N-terminal kinase (JNK)/stress activated protein kinase-associated protein 1, JSAP1
  • NCK adaptor protein 2, NCK2
  • activates Src family kinases via c-Src SH2/SH3 interactions
  • triple functional domain (PTPRF interacting), TRIO
  • protein inhibitor of activated STAT 1, PIAS1
  • calcium- and integrin-binding protein, CIB
  • potassium large conductance calcium-activated channel subfamily M alpha member 1, KCNMA1
  • death domain kinase receptor-interacting protein, RIP
  • netrin 1, NTN1
  • N-terminal transactivation domain of p53
  • dynamin
  • SAP90/PSD-95-Associated Protein-3, SAPAP3
  • EPH receptor B2, EPHB2
  • vascular endothelial growth factor receptor-3, VEGFR3
  • tuberous sclerosis complex 2, TSC2
  • CAS family members and with GIT1, SORBS1 and BCAR3
  • MAPK7
  • ARHGAP21 interacts with the C-terminal region of Focal Adhesion Kinase (PTK2)
  • IGF1R (role in phosphorylation, signaling and stability of the IGF1R)
  • binding-protein partner for ELK1, a finding that significantly broadens the potential functioning of PTK2 and ELK1
  • with ARHGEF11 and ROCK2, cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts
  • DLGAP3 and ASAP1
  • PTK2 binds the pleckstrin homology domain of AGAP2, and the binding is independent of PTK2 activation following epidermal growth factor receptor stimulation
  • IGF1R and plays an important role in cancer cell survival
  • epithelial membrane protein 2, EMP2
  • GNB1-mediated FYN activation integrates PTK2 with adherens junctions, preventing persistent endothelial barrier leakiness
  • interactio with CADM1 (PTK2 is its binding partner and effector in shaping growth cones)
  • interacting with XIAP (XIAP modulates PTK2 activity through the control of PTK2 phosphorylation)
  • scaffold and tyrosine kinase protein that binds to itself and cellular partners through its four-point-one, ezrin, radixin, moesin (FERM) domain
  • ZG16B-mediated PTK2 activation plays an important role in pancreatic cancer progression
  • PTK2 modulates radial glia-dependent neuronal migration through GJB2
  • suppression of vimentin intermediate filaments by PTK2 facilitates the assembly of podosome rosettes
  • DLC1 binds to the FAT domain of PTK2 through at least some of the FAT sequences that bind paxillin, although it remains possible that other regions of PTK2 may also interact with DLC1
  • PTK2 is a novel regulator of SNAIL1-dependent epithelial-mesenchymal transition in embryonic cells
  • ABCB1 is involved in regulating BTB dynamics, likely via its interaction with PTK2, which modulates the phosphorylation status of the OCLN/TJP1 protein complex
  • alternative linkage for PTK2-talin interactions within nascent adhesions essential for the control of cell migrationv
  • modulates CDC42 activity downstream of positive and negative axon guidance cues
  • XIAP plays a key role in vascular functions of PTK2B or PTK2B domain-mediated vascular functions of PTK2
  • cell spreading promotes the association of cortactin and PTK2 and tyrosine phosphorylation of CTTN disrupts this interaction, which may explain how it inhibits cell spreading
  • NANOG binds the PTK2 promoter, up-regulates PTK2, and directly binds and is phosphorylated by PTK2 that regulates cell morphology, growth, and invasion
  • binds and phosphorylates wild type NANOG protein but not the mutant NANOG with Y35F and Y174F mutations
  • is a critical intracellular adaptor for ADAM15-dependent enhancement of PTK2/SRC activation
  • PTK2 inhibition resulted in the loss of the GATA4 transcription factor required for TNF-induced VCAM1 production
  • contributes to cytokine signaling and bone resorption in osteoclasts and partially compensates for the absence of PTK2B to maintain proper adhesion structures in these cells
  • stabilizes focal adhesion signaling in the absence of adhesion, as assessed by reduced caspase-dependent cleavage of PTK2 following cell detachment and sustained activity of the AKT1 signaling pathway
  • important roles for a PTK6-PTK2-AKT1 signaling axis in promoting anchorage-independent cell survival
  • is a critical downstream regulator of GRPR, which mediates tumorigenesis and metastasis in neuroblastoma
  • STK11 serves as a PTK2 repressor to stabilize focal adhesion sites
  • link between PTK2 and BMP4 induction of mesenchymal stem cells (MSCs) adipogenesis, and may indicate a potential therapeutic approach targeting PTK2 for dealing with obesity
  • THOC2 can play specific roles in neuronal cells and, possibly in combination with PTK2 reduction, may affect normal neural network formation, leading to cognitive impairment and cerebellar congenital hypoplasia
  • GNB2L1 scaffolds AGAP2 to PTK2 to regulate PTK2 activity and cell adhesion during the differentiation process
  • GRB2 is a new PTK2 activator awith an essential role in coordinating PTPRA tyrosine phosphorylation to enable downstream integrin signaling and migration
  • ETV4 is able to transactivate PTK2 expression through binding to the promoter region of PTK2
  • PTK2 negatively regulates LCK function downstream of the T cell antigen receptor
  • TRIM72 induces PTK2 ubiquitination with the aid of UBE2H during skeletal myogenesis
  • is a novel positive regulator of cellular protrusion formation and neurite outgrowth through the PTK2 signaling pathway
  • interaction between ARHGEF28 and PTK2, a non-receptor tyrosine kinase that controls migration properties of normal and tumor cells
  • LAMA2-mediated PTK2 activation in podocytes is an important early event in Alport glomerular pathogenesis
  • RACGAP1 promoted the activations of RHOA, PTK2, PXN and triggered focal adhesion formation and cytoskeletal rearrangement
  • CA8 might facilitate cancer cell invasion via the activation of PTK2-MMP9 signaling
  • TGFB1I1 appears to enhance complex formation between MMP14 and PTK2 in activated endothelial cells, which likely coordinates matrix proteolysis and cell motility
  • PTK2B, but not PTK2, could directly phosphorylate PYCARD at Tyr146, and only the phosphorylated PYCARD could participate in speck formation and trigger IL1B secretion
  • MARVELD1 regulated neuronal migration by mediating the formation of glial fibres and ITGB1/PTK2 signalling pathway
  • cell & other
    REGULATION
    activated by tyrosine-phosphorylation in response to either integrin clustering or via G-protein coupled receptor (GPCR) occupancy by ligands such as bombesin or lysophosphatidic acid, or via LDL receptor occupancy
    integrin LFA-1
    Other acetylation
    phosphorylated via integrins or growth factor receptors
    phosphorylated by tyrosine aminotransferase, Tat
    phosphorylated bythrombin
    phosphorylated by EMP2 overexpression
    phosphorylated by ret proto-oncogene
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma
    constitutional fusion      
    PTK2-THOC2 gene fusion in a patient with psychomotor retardation and congenital cerebellar hypoplasia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    targeting interaction PTK2/IGF1R with small molecules is a novel strategy for treatment of pancreatic cancer or other cancers
    miscelleaneousurinary 
    FAK inhibitors, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages
    ANIMAL & CELL MODELS
  • FAK-deficient mice display a general defect of mesoderm development, and cells from these embryos have reduced mobility in vitro
  • Null mutation of FAK results in embryonic lethality, and FAK-/- fibroblasts exhibit cell migration defects in culture
  • keratinocyte cell death was observed after fak deletion in vitro and in vivo in mice
  • mice in which FAK is selectively inactivated in cardiomyocytes develop eccentric cardiac hypertrophy ncreased heart/body weight ratios, elevated markers of cardiac hypertrophy, multifocal interstitial fibrosis, and increased collagen I and VI expression
  • focal adhesion kinase (FAK) conditional knockout mice display Cardiac developmental defects and eccentric right ventricular hypertrophy