Summary
Basic Information
Immunogen
Monoclonal antibody is produced by immunizing animals with a GST-Pyk2 fusion protein containing residues surrounding the carboxy-terminal of human Pyk2.
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Buffer
100 µg/ml BSA, 50% glycerol
Preservative
0.02% sodium azide
Purity
> 95% Purity determined by SDS-PAGE.
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.
Target
Function
Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca2+ levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2.
Biological Process
Activation of GTPase activityIEA:Ensembl
Activation of Janus kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Adaptive immune responseIEA:UniProtKB-KW
Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Blood vessel endothelial cell migrationIEA:Ensembl
Bone resorptionISS:UniProtKB
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cell surface receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Cellular defense responseISS:Alzheimers_University_of_Toronto
Cellular response to fluid shear stressIEA:Ensembl
Cellular response to retinoic acidManual Assertion Based On ExperimentIMP:BHF-UCL
Chemokine-mediated signaling pathwayISS:UniProtKB
Endothelin receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Epidermal growth factor receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Focal adhesion assemblyIEA:Ensembl
Glial cell proliferationIEA:Ensembl
Innate immune responseManual Assertion Based On ExperimentIBA:GO_Central
Integrin-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Ionotropic glutamate receptor signaling pathwayISS:Alzheimers_University_of_Toronto
Long-term synaptic depressionIEA:Ensembl
Long-term synaptic potentiationISS:Alzheimers_University_of_Toronto
MAPK cascadeIEA:Ensembl
Marginal zone B cell differentiationISS:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of bone mineralizationISS:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of muscle cell apoptotic processIEA:Ensembl
Negative regulation of myeloid cell differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of neuron apoptotic processISS:Alzheimers_University_of_Toronto
Negative regulation of potassium ion transportManual Assertion Based On ExperimentIDA:UniProtKB
Neuron projection developmentIEA:Ensembl
Oocyte maturationIEA:Ensembl
Peptidyl-tyrosine autophosphorylationManual Assertion Based On ExperimentIDA:CACAO
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of actin filament polymerizationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of angiogenesisIEA:Ensembl
Positive regulation of B cell chemotaxisISS:UniProtKB
Positive regulation of cell growthIEA:Ensembl
Positive regulation of cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cell-matrix adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cytosolic calcium ion concentrationIEA:Ensembl
Positive regulation of DNA biosynthetic processIEA:Ensembl
Positive regulation of endothelial cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of excitatory postsynaptic potentialISS:Alzheimers_University_of_Toronto
Positive regulation of JNK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JUN kinase activityIEA:Ensembl
Positive regulation of neuron projection developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of nitric oxide biosynthetic processIEA:Ensembl
Positive regulation of nitric-oxide synthase activityIEA:Ensembl
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phosphatidylinositol 3-kinase activityISS:UniProtKB
Positive regulation of protein kinase activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of reactive oxygen species metabolic processIEA:Ensembl
Positive regulation of synaptic transmission, glutamatergicISS:Alzheimers_University_of_Toronto
Positive regulation of translationIEA:Ensembl
Positive regulation of ubiquitin-dependent protein catabolic processIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentTAS:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Protein-containing complex assemblyManual Assertion Based On ExperimentTAS:ProtInc
Regulation of actin cytoskeleton reorganizationISS:UniProtKB
Regulation of calcium-mediated signalingIEA:Ensembl
Regulation of cell adhesionManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cell shapeManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of cGMP-mediated signalingIEA:Ensembl
Regulation of establishment of cell polarityISS:UniProtKB
Regulation of inositol trisphosphate biosynthetic processISS:UniProtKB
Regulation of macrophage chemotaxisISS:UniProtKB
Regulation of NMDA receptor activityISS:Alzheimers_University_of_Toronto
Regulation of release of sequestered calcium ion into cytosolISS:UniProtKB
Regulation of synaptic plasticityManual Assertion Based On ExperimentTAS:ARUK-UCL
Regulation of ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Response to calcium ionIEA:Ensembl
Response to cAMPIEA:Ensembl
Response to cation stressIEA:Ensembl
Response to cocaineIEA:Ensembl
Response to ethanolIEA:Ensembl
Response to glucoseIEA:Ensembl
Response to hormoneIEA:Ensembl
Response to hydrogen peroxideIEA:Ensembl
Response to hypoxiaIEA:Ensembl
Response to immobilization stressIEA:Ensembl
Response to ischemiaIEA:Ensembl
Response to lithium ionIEA:Ensembl
Response to mechanical stimulusIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Signal complex assemblyManual Assertion Based On ExperimentTAS:ProtInc
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Sprouting angiogenesisISS:UniProtKB
Stress fiber assemblyIEA:Ensembl
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Vascular endothelial growth factor receptor signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Cellular Location
Cytoplasm
Cytoplasm, perinuclear region
Cell membrane
Cell junction, focal adhesion
Cell projection, lamellipodium
Cytoplasm, cell cortex
Nucleus
Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with integrins at the cell periphery.
Involvement in disease
Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.
PTM
Phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration; this activation is indirect and may be mediated by production of reactive oxygen species (ROS). Tyr-402 is the major autophosphorylation site, but other kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-402 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is important for interaction with GRB2. Phosphorylated on tyrosine residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell matrix adhesions initiates Tyr-402 phosphorylation. In monocytes, adherence to substrata is required for tyrosine phosphorylation and kinase activation. Angiotensin II, thapsigargin and L-alpha-lysophosphatidic acid (LPA) also induce autophosphorylation and increase kinase activity. Phosphorylation by MYLK promotes ITGB2 activation and is thus essential to trigger neutrophil transmigration during lung injury. Dephosphorylated by PTPN12.