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EGF Signaling: Tracking the path of Cancer
The epidermal growth factor (EGF) family is a group of structurally related proteins that regulate cell proliferation, migration and differentiation through tyrosine kinase receptors on target cells. EGF receptors have a cytoplasmic tyrosine kinase domain, a transmembrane domain, and an extracellular domain that binds to EGF. Binding of the ligand to the EGF receptor results in dimerization, autophosphorylation, and activation. Once activated, EGF receptors transmit intracellular signals through the phosphorylation of several proteins.
Activation of Ras by EGF receptors is an important component of EGF signaling. The guanine nucleotide exchange factor SOS activates Ras, which in turn triggers the mitogen-activated protein (MAP) kinase pathway. MAP kinases phosphorylate transcription factors such as activator protein 1 (AP-1; Fos-Jun dimer) and Elk-1, leading to cell growth and development. Phosphorylation of Janus kinase (JAK) by EGFR leads to activation of transcriptional protein signal transducers and activators (STATs), ultimately leading to cell growth and differentiation. Another key aspect of EGF signaling involves the phospholipase c-γ1 (PLCγ1), which cleaves PIP2 into IP3 and DAG. IP3 production leads to ER calcium release, whereas DAG promotes protein kinase C (PKC) activation. PKC in turn phosphorylates and activates the transcription factor Elk-1, leading to cell proliferation. Mutations in EGFR are known to affect its expression or activity, making EGFR an important drug target.
This pathway highlights an important component of EGF signaling.
Emphasis on epidermal growth factor signaling pathway
Gene Symbol | Name | Cellular Functions | Disease Associations | Subcellular Locations | Upstream Regulators | Binding Partners | Downstream Interactors | Antibodies | Small Molecules |
STAT3 | signal transducer and activator of transcription 3 (acute-phase response factor) | proliferation apoptosis expression in transformation differentiation | tumorigenesis obesity enterocolitis Crohn’s Disease hyperphagia | nucleus cytoplasm focal adhesions nuclear foci plasma membrane | IL6 IL10 IL2 IL21 Interferon Alpha | FOS EGFR PRKCD DIRAS3 IL2RB | TERT IL10 HIF1A CDKN1A SOCS3 | Anti-STAT3 antibody produced in goat | ? |
EGFR | epidermal growth factor receptor | proliferation | cancer | cell surface | EGF | EGF | Mapk | Monoclonal Anti-EGF Receptor antibody produced in mouse | Inhibitor: CP-380736 |
c-Raf | v-raf-1 murine leukemia viral oncogene homolog 1 | transformation | transformation proliferation | cytoplasm | EGF | HRAS | MAPK1 | Monoclonal Anti-Raf-1/c-Raf antibody produced in mouse | GW5074 |
JNK1 | mitogen-activated protein kinase 8 | apoptosis | tumorigenesis | nucleus | TNF | JUN | CDKN1B | Monoclonal Anti-JNK antibody produced in mouse | Inhibitor: SP600125 |
c-Jun | jun proto-oncogene | apoptosis | tumorigenesis | nucleus ? | TNF | FOS ? | HIF1A | Anti-JUN(Ab-91) antibody produced in rabbit | ? |
PKCα | protein kinase C, alpha | apoptosis | neurodegenerative disease | cytoplasm nucleus | phosphatidylserine | ITGB1 | Erk1/2 | Monoclonal Anti-PRKCA antibody produced in mouse | Inhibitor: K-252a |
STAT1 | signal transducer and activator of transcription 1, 91kDa | apoptosis | infection | nucleus | IFNG | EIF2AK2 | IRF1 | Anti-STAT1(Ab-701) antibody produced in rabbit | ? |
EGF | epidermal growth factor | proliferation | Alzheimer’s Disease | apical membrane | ERBB2 | EGFR | EGFR | Monoclonal Anti-Epidermal Growth Factor antibody produced in mouse | Inhibitor: Suramin sodium salt |
GRB2 | growth factor receptor-bound protein 2 | growth | Crohn’s disease | centrosome | F2 ? | SHC1 ? | MAPK3 ? | Anti-GRB2 antibody produced in goat | ? |
MEK1 | mitogen-activated protein kinase kinase1 | apoptosis | tumorigenesis | cytoplasm | EGF | MAPK1 | MLANA | Anti-MEK1 antibody produced in rabbit | Inhibitor: PD98,059 |
hRas | v-Ha-ras Harvey rat sarcoma viral oncogene homolog | transformation | tumorigenesis | nucleus | Cd3 | RAF1 | reactive oxygen | Anti-RASH，N-Terminal antibody produced in rabbit | Antagonist: Erastin |
c-Fos | FBJ murine osteosarcoma viral oncogene homolog | transformation | cancer | nucleus | beta-estradiol | JUN | IL6 | Anti-FOS antibody produced in rabbit |
References
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