HomeCancer ResearchEGF Signaling: Tracing Cancer's Path

EGF Signaling: Tracing Cancer's Path

Biowire Fall 2011 — Screening — microRNA Target Identification

The epidermal growth factor (EGF) family is a group of structurally related proteins that regulate cell proliferation, migration and differentiation via tyrosine kinase receptors on target cells. The EGF receptor has a cytoplasmic tyrosine kinase domain, a transmembrane domain and an extracellular domain that binds to EGF. Ligand binding to the EGF receptor results in its dimerization, autophosphorylation and activation. Once activated, the EGF receptor transmits intracellular signals via the phosphorylation of several proteins.

The activation of Ras by the EGF receptor is an important component in EGF signaling. The guanine nucleotide exchange factor SOS activates Ras, which in turn triggers the mitogenactivated protein (MAP) kinase pathway. MAP kinases phosphorylate transcription factors like activator protein 1 (AP-1; Fos-Jun dimer) and Elk-1, leading to cellular growth and development. The phosphorylation of Janus kinases (JAK) by EGFR results in the activation of Signal Transducer and Activator of Transcription proteins (STATs) which ultimately lead to cell growth and differentiation. Another key aspect of EGF signaling involves Phospholipase C-gamma 1 (PLCγ1), which cleaves PIP2 into IP3 and DAG. IP3 production results in endoplasmic reticulum calcium release while DAG promotes the activation of Protein Kinase C (PKC). PKC in turn phosphorylates and activates the transcription factor Elk-1 which leads to cellular proliferation. Mutations in EGFR affecting its expression or activity are known to be involved in cancers, making EGFR an important drug target.

This pathway highlights the important components of EGF signal transduction.

Highlights from the EGF Signaling Pathway

Find additional annotations and products for this pathway

Find additional annotations and products for this pathway at



Corbalan-Garcia S, Margarit SM, Galron D, Yang S, Bar-Sagi D. 1998. Regulation of Sos Activity by Intramolecular Interactions. Mol. Cell. Biol.. 18(2):880-886.
Russell M, Lange-Carter CA, Johnson GL. 1995. Direct Interaction between Ras and the Kinase Domain of Mitogen-activated Protein Kinase Kinase Kinase (MEKK1). Journal of Biological Chemistry. 270(20):11757-11760.
Ackerman P, Glover CV, Osheroff N. 1990. Stimulation of casein kinase II by epidermal growth factor: relationship between the physiological activity of the kinase and the phosphorylation state of its beta subunit.. Proceedings of the National Academy of Sciences. 87(2):821-825.
Andl CD, Mizushima T, Oyama K, Bowser M, Nakagawa H, Rustgi AK. 2004. EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. American Journal of Physiology-Gastrointestinal and Liver Physiology. 287(6):G1227-G1237.
Baker SJ, Kerppola TK, Luk D, Vandenberg MT, Marshak DR, Curran T, Abate C. 1992. Jun is phosphorylated by several protein kinases at the same sites that are modified in serum-stimulated fibroblasts.. Mol. Cell. Biol.. 12(10):4694-4705.
Takekawa M, Tatebayashi K, Saito H. 2005. Conserved Docking Site Is Essential for Activation of Mammalian MAP Kinase Kinases by Specific MAP Kinase Kinase Kinases. Molecular Cell. 18(3):295-306.
Chong M, Barritt G, Crouch M. 2004. Insulin potentiates EGFR activation and signaling in fibroblasts. Biochemical and Biophysical Research Communications. 322(2):535-541.
Krug AW, Schuster C, Gassner B, Freudinger R, Mildenberger S, Troppmair J, Gekle M. 2002. Human Epidermal Growth Factor Receptor-1 Expression Renders Chinese Hamster Ovary Cells Sensitive to Alternative Aldosterone Signaling. Journal of Biological Chemistry. 277(48):45892-45897.
Lim CP, Cao X. 1999. Serine Phosphorylation and Negative Regulation of Stat3 by JNK. Journal of Biological Chemistry. 274(43):31055-31061.
Diakonova M, Payrastre B, van Velzen AG, Hage W, van Bergen en Henegouwen PM, Boonstra J, Cremers F, Humbel B. 1995. Epidermal growth factor induces rapid and transient association of phospholipase C-gamma 1 with EGF-receptor and filamentous actin at membrane ruffes of A431 cells.. J Cell Sci..(108):2499–2509.
Eldar H, Zisman Y, Ullrich A, Livneh E. 1990. Overexpression of protein kinase C alpha-subtype in Swiss/3T3 fibroblasts causes loss of both high and low affinity receptor numbers for epidermal growth factor.. Journal of Biological Chemistry. 265(22):13290-13296.
Weston CR, Wong A, Hall JP, Goad MEP, Flavell RA, Davis RJ. 2004. The c-Jun NH2-terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis. Proceedings of the National Academy of Sciences. 101(39):14114-14119.
Carpenter G, Cohen S. 1990. Epidermal growth factor.. Journal of Biological Chemistry. 265(14):7709-7712.
Hu, Bowtell D. 1996. Sos1 rapidly associates with Grb2 and is hypophosphorylated when complexed with the EGF receptor after EGF stimulation. Oncogene.. 12(9):1865–72.
Ueno H, Sasaki K, Miyagawa K, Honda H, Mitani K, Yazaki Y, Hirai H. 1997. Antisense Repression of Proto-oncogene c-Cbl Enhances Activation of the JAK-STAT Pathway but Not the Ras Pathway in Epidermal Growth Factor Receptor Signaling. Journal of Biological Chemistry. 272(13):8739-8743.
Cummins AB, Palmer C, Mossman BT, Taatjes DJ. 2003. Persistent Localization of Activated Extracellular Signal-Regulated Kinases (ERK1/2) Is Epithelial Cell-Specific in an Inhalation Model of Asbestosis. The American Journal of Pathology. 162(3):713-720.
Yoshikawa S, Tanimura T, Miyawaki A, Nakamura M, Yuzaki M, Furuichi T, Mikoshiba K. 1992. Molecular cloning and characterization of the inositol 1,4,5-trisphosphate receptor in Drosophila melanogaster.. Journal of Biological Chemistry. 267(23):16613-16619.
Mahimainathan L, Ghosh-Choudhury N, Venkatesan BA, Danda RS, Choudhury GG. 2005. EGF stimulates mesangial cell mitogenesis via PI3-kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27Kip1. American Journal of Physiology-Renal Physiology. 289(1):F72-F82.
Xia Y, Makris C, Su B, Li E, Yang J, Nemerow GR, Karin M. 2000. MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration. Proceedings of the National Academy of Sciences. 97(10):5243-5248.
Chen D, Davis JS. 2003. Epidermal growth factor induces c-fos and c-jun mRNA via Raf-1/MEK1/ERK-dependent and -independent pathways in bovine luteal cells. Molecular and Cellular Endocrinology. 200(1-2):141-154.
Sign In To Continue

To continue reading please sign in or create an account.

Don't Have An Account?