Epidermal growth factor receptor (EGFR) is a 170 kDa transmembrane glycoprotein receptor tyrosine kinase that, activated by epidermal growth factor (EGF), affects cell growth and differentiation (1). Binding of EGF or TGF alpha to EGFR activates tyrosine kinase activity of the receptor (2). Phosphorylation of Tyr 992, Tyr 1068 and Tyr 1086 is required for conformational change in the C-terminal of EGFR (3). Autophosphorylation of Tyr 992 creates a binding site for the phospholipase C-gamma (PLCgamma) SH2 domain, inducing downstream signaling (4).
Product Information
Format
Unpurified
Control
A431 cell lysate
Presentation
Rabbit Monoclonal in buffer containing glycerol, BSA, and sodium azide.
Applications
Application
Please note that this product will not be available for sale after March 15, 2015. Please select one of the other antibodies against this target.
Key Applications
Immunohistochemistry
Western Blotting
Immunocytochemistry
Immunoprecipitation
Application Notes
Immunohistochemistry Analysis: A 1:10-25 dilution from a representative lot was used in human cervical carcinoma tissue.
Immunocytochemistry Analysis: A 1:10 dilution from a representative lot was used in IC.
Immunoprecipitation Analysis: A 1:10 dilution from a representative lot was used in IP.
Biological Information
Immunogen
Synthetic peptide corresponding to the C-terminus of human EGFR.
FUNCTION:Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.
Isoform 2 may act as an antagonist of EGF action. CATALYTIC ACTIVITY:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION:Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling. SUBUNIT STRUCTURE:Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL; involved in EGFR ubiquitination and regulation. Interacts with SOCS5; regulates EGFR degradation through TCEB1- and TCEB2-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5; methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG; essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2; this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May interact with EPS8; mediates EPS8 phosphorylation. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. SUBCELLULAR LOCATION:Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Nucleus membrane; Single-pass type I membrane protein. Endosome. Endosome membrane. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand.
Isoform 2: Secreted TISSUE SPECIFICITY:Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. PTM:Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3.
Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occur.
Methylated. Methylation at Arg-1199 by PRMT5 positively stimulates phosphorylation at Tyr-1197. Ref.66 INVOLVEMENT IN DISEASEDefects in EGFR are associated with lung cancer (LNCR) [MIM:211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. SEQUENCE SIMILARITIES:Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Contains 1 protein kinase domain.
Product Usage Statements
Quality Assurance
Evaluated by Western Blot in A431 cell lysate.
Western Blot Analysis: A 1:1,000-10,000 dilution of this antibody detected EGFR in A431 cell lysate.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 1 year at -20ºC from date of receipt.
Handling Recommendations: Upon first thaw, and prior to removing cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20ºC. Avoid freeze/thaw cycles, which may damage IgG and affect product performance.
Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage. Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage.
Epidermal growth factor receptor (EGFR) is a 170 kDa transmembrane glycoprotein receptor tyrosine kinase that, activated by epidermal growth factor (EGF), affects cell growth and differentiation (1). Binding of EGF or TGF alpha to EGFR activates tyrosine kinase activity of the receptor (2). Phosphorylation of Tyr 992, Tyr 1068 and Tyr 1086 is required for conformational change in the C-terminal of EGFR (3). Autophosphorylation of Tyr 992 creates a binding site for the phospholipase C-gamma (PLCgamma) SH2 domain, inducing downstream signaling (4).
Product Information
Format
Unpurified
Control
A431 cell lysate
Presentation
Rabbit Monoclonal in buffer containing glycerol, BSA, and sodium azide.
Applications
Application
Please note that this product will not be available for sale after March 15, 2015. Please select one of the other antibodies against this target.
Key Applications
Immunohistochemistry
Western Blotting
Immunocytochemistry
Immunoprecipitation
Application Notes
Immunohistochemistry Analysis: A 1:10-25 dilution from a representative lot was used in human cervical carcinoma tissue.
Immunocytochemistry Analysis: A 1:10 dilution from a representative lot was used in IC.
Immunoprecipitation Analysis: A 1:10 dilution from a representative lot was used in IP.
Biological Information
Immunogen
Synthetic peptide corresponding to the C-terminus of human EGFR.
FUNCTION:Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.
Isoform 2 may act as an antagonist of EGF action. CATALYTIC ACTIVITY:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION:Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling. SUBUNIT STRUCTURE:Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL; involved in EGFR ubiquitination and regulation. Interacts with SOCS5; regulates EGFR degradation through TCEB1- and TCEB2-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5; methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG; essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2; this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. May interact with EPS8; mediates EPS8 phosphorylation. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. SUBCELLULAR LOCATION:Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Nucleus membrane; Single-pass type I membrane protein. Endosome. Endosome membrane. Note: In response to EGF, translocated from the cell membrane to the nucleus via Golgi and ER. Endocytosed upon activation by ligand.
Isoform 2: Secreted TISSUE SPECIFICITY:Ubiquitously expressed. Isoform 2 is also expressed in ovarian cancers. PTM:Phosphorylation at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3.
Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occur.
Methylated. Methylation at Arg-1199 by PRMT5 positively stimulates phosphorylation at Tyr-1197. Ref.66 INVOLVEMENT IN DISEASEDefects in EGFR are associated with lung cancer (LNCR) [MIM:211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. SEQUENCE SIMILARITIES:Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Contains 1 protein kinase domain.
Product Usage Statements
Quality Assurance
Evaluated by Western Blot in A431 cell lysate.
Western Blot Analysis: A 1:1,000-10,000 dilution of this antibody detected EGFR in A431 cell lysate.
Usage Statement
Unless otherwise stated in our catalog or other company documentation accompanying the product(s), our products are intended for research use only and are not to be used for any other purpose, which includes but is not limited to, unauthorized commercial uses, in vitro diagnostic uses, ex vivo or in vivo therapeutic uses or any type of consumption or application to humans or animals.
Storage and Shipping Information
Storage Conditions
Stable for 1 year at -20ºC from date of receipt.
Handling Recommendations: Upon first thaw, and prior to removing cap, centrifuge the vial and gently mix the solution. Aliquot into microcentrifuge tubes and store at -20ºC. Avoid freeze/thaw cycles, which may damage IgG and affect product performance.
Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage. Note: Variability in freezer temperatures below -20°C may cause glycerol containing solutions to become frozen during storage.
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