Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. (genome.jp)
EGFR is type I receptor tyrosine kinase with sequence homology to erbB-1, -2, -3 -4 or HER-1, -2, -3 -4. (neobiotechnologies.com)
Phosphorylation of EGFR at certain residues is also mediated by Src-non-receptor kinase. (thermofisher.com)
EGFR activation signals multiple downstream signaling cascades such as the Ras - ERK, PI3-K - Akt, Jak - STAT and PKC pathways that help in growth and proliferation of cells. (thermofisher.com)
Phosphorylation of EGFR at Y1086 specifically allows binding of the adaptor protein GRB2, leading to activation of the MAPK pathway. (thermofisher.com)
Upon receptor activation and signaling, EGFR is endocytosed and targeted for degradation or recycling. (thermofisher.com)
The epidermal growth factor receptor (EGFR) is a member of the ErbB family that can promote the migration and proliferation of breast cancer cells. (uzh.ch)
Therapies that target EGFR can promote the dimerization of EGFR with other ErbB receptors, which is associated with the development of drug resistance. (uzh.ch)
Understanding how interactions among ErbB receptors alter EGFR biology could provide avenues for improving cancer therapy. (uzh.ch)
The CYT2 variant, but not the CYT1 variant, protected EGFR from ligand-induced degradation by competing with EGFR for binding to a complex containing the E3 ubiquitin ligase c-Cbl and the adaptor Grb2. (uzh.ch)
In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways. (nih.gov)
Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. (nih.gov)
Adaptor proteins, GRB2 and SOS, are then sequentially recruited to stimulate the release of GDP from KRAS which permits binding of GTP to activate KRAS. (hindawi.com)
Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. (genome.jp)
The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. (neobiotechnologies.com)
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 (PubMed:11602604). (neobiotechnologies.com)
This revealed which proteins had changed location, identifying these proteins as important for the cell's response to the growth factor. (elifesciences.org)
Comparison of the binding activity of the JNK isoforms demonstrated that the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors. (umassmed.edu)
Despite the close relationship between the Drosophila and mammalian Shc proteins, dShc lacks the high-affinity Grb2-binding site found in mammalian Shc, suggesting that Shc proteins may have functions in addition to regulation of the Ras pathway. (elsevierpure.com)
Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. (icr.ac.uk)
FGFRs are a class of receptor tyrosine kinase (RTK) and are single-pass membrane proteins made of N-terminal extracellular (EC) domains with three immunoglobulin-like subdomains (D1, D2 and D3), a transmembrane (TM) domain with a single α-helix, and an intracellular (IC) region which includes tyrosine kinase motifs, a juxta-membrane domain and a carboxyl-terminal tail [12-14]. (123dok.org)
In addition to plexins, various other proteins have been implicated either as receptors for semaphorins or as components of the semaphorin receptor complex ( Pasterkamp and Kolodkin, 2003 ). (rupress.org)
The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. (genome.jp)
The combination of growth factors and RTKs can activate the PI3K/AKT signaling pathway and negatively regulate TSC1/2, promoting Rheb to become GTP loaded, which can activate mTORC1. (biomedcentral.com)
Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. (123dok.org)
Ligands4
The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. (genome.jp)
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:2790960, PubMed:10805725, PubMed:27153536). (neobiotechnologies.com)
Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands. (uchicago.edu)
Tyrosine phosphorylation of GRB2 SH3 domains reduces binding to Sos and negatively regulates downstream signaling pathways including Ras, JNK and MAPK. (rndsystems.com)
Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression. (uchicago.edu)
Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosinephosphorylation of its cognate receptor, Met. (spandidos-publications.com)
Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
Kinase6
BRAF is a protein kinase and part of the MAP kinase signalling cascade which involves transduction of a growth signal from the cell membrane to the nucleus via a chain of protein kinases and is responsible for cellular proliferation and survival. (hindawi.com)
The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. (umassmed.edu)
In addition to a C-terminal Src homology 2 (SH2) domain, dShc contains an N-terminal phosphotyrosine-binding (PTB) domain, which associates in vitro with the autophosphorylated DER receptor tyrosine kinase and with phosphopeptides containing an Asn-Pro-X-pTyr motif, where pTyr stands for phosphotyrosine. (elsevierpure.com)
Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. (icr.ac.uk)
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. (univ-amu.fr)
Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
Fibroblast growth f1
Among such actionable targets in BC is the fibroblast growth factor receptor (FGFR). (123dok.org)
Interaction2
Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth. (uchicago.edu)
Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. (rupress.org)
Adapter protein2
an adapter protein coupling the receptor to downstream signaling pathways. (bioss.com.cn)
Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. (bomiprot.org)
Pathways2
The SH3 domains associate with proline rich motifs on the guanine nucleotide releasing factor, Sos, stimulating GTP binding to Ras, which in turn activates MAPK and other signaling pathways. (rndsystems.com)
Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. (genome.jp)
ErbB2
We propose a mechanism whereby competition for binding to c-Cbl in an ErbB signaling heterodimer promotes migration in response to a growth factor gradient. (uzh.ch)
A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. (rupress.org)
MAPK1
An activating hotspot mutation occurs at V600E and results in constitutive MAPK signalling and uncontrolled cellular growth. (hindawi.com)
Guanine1
GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. (nih.gov)
Homolog1
In flies, the dShc protein physically associates with the activated Drosophila epidermal growth factor receptor homolog (DER) and is inducibly phosphorylated on tyrosine by DER. (elsevierpure.com)
Homo2
Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. (neobiotechnologies.com)
Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. (bioss.com.cn)
Substrate1
In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. (nih.gov)
Gene2
Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) ( 9 ). (spandidos-publications.com)
Elimination of the primary tumor, either by irradiation or by surgery, shifts the balance towards pro-angiogenesis and growth of the lung metastases (Table 1 ) (Camphausen et al. (biomedcentral.com)
Hypoxia stimulates hypoxia inducible factor (HIF)-dependent expression of CXCL12 and KITL promoting mobilization from the bone marrow and recruitment to primary tumor and metastatic sites of CXCR4 + CD11b + bone marrow-derived cells and KITbCD11b + cells assisting vasculogenesis and metastasis respectively (Kuonen et al. (biomedcentral.com)
Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. (icr.ac.uk)
Isoform1
some are promiscuous, such as FGF1, and bind to multiple receptors, while others, such as FGF7, tether only one receptor isoform [11]. (123dok.org)
Antigen2
CBL-B expression in T cells causes ligand-induced T cell receptor down-modulation, controlling the activation degree of T cells during antigen presentation. (wikipedia.org)
Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha. (uchicago.edu)
Ligand3
Such treatment was associated with upregulation of invasion- and inflammation-promoting soluble factors, such as matrix metalloproteinase 2 (MMP2), its activator MMP14, tissue inhibitors of matrix metalloproteinase 2 (TIMP2), chemokine ligand 2 (CCL2), and urokinase-type plasminogen activator (uPA), the latter two being linked to the recruitment of the monocytic cells. (biomedcentral.com)
Furthermore, immunoglobulin-like subdomains D2 and D3 are necessary and sufficient for ligand binding, whereas the aminoterminal part of the receptor-including D1-has an auto-inhibitory function [16]. (123dok.org)
Drosophila2
These data revealed an unexpected direct binding of Corkscrew, the Drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e , the human ortholog of the p110 catalytic subunit. (sdbonline.org)
The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (human GAB2 but not Drosophila Dos ). (sdbonline.org)
Transcription factors1
Individual members of the JNK group may therefore selectively target specific transcription factors in vivo. (umassmed.edu)
Cell migration1
Mutation of these residues in the dimer interface destabilized the complex in cells and abrogated growth factor-stimulated cell migration. (uzh.ch)
Complexes2
Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. (neobiotechnologies.com)
Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2. (icr.ac.uk)
Bound1
GRB2 (growth factor receptor-bound protein 2), an adaptor protein involved in signal transduction, contains a central SH2 domain flanked by two SH3 domains. (rndsystems.com)
Plasma membrane1
5) Lysosomes can also fuse with the plasma membrane to mediate membrane repair or discharge contents outside the cell, such as cathepsins or immune factors. (biomedcentral.com)