EGF Receptor Signal Transduction Pathway

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EGF Receptor Signal Transduction Pathway
SIGMA-ALDRICH
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EGF Receptor Signal Transduction Pathway The
epidermal growth factor (EGF) family of receptor
tyrosine kinases consists of four receptors,
EGF-R (ErbB1), ErbB2 (Neu), ErbB3, and ErbB4.
Members of the EGF-R family contain a cytoplasmic
tyrosine kinase domain, a single transmembrane
domain, and an extracellular domain that is
involved in ligand binding and receptor
dimerization. Activation of the EGF-R results in
the initiation of a diverse array of cellular
pathways. In response to toxic environmental
stimuli, such as ultraviolet irradiation, or to
receptor occupation by EGF, the EGF-R forms homo-
or heterodimers with other family members. Each
dimeric receptor complex will initiate a distinct
signaling pathway by recruiting different Src
homology 2 (SH2)-containing effector proteins.
Dimerization results in autophosphorylation
initiating a downstream cascade of events
culminating in cellular responses such as cell
proliferation or apoptosis. The activated EGF-R
dimer complexes with the adaptor protein, Grb,
coupled to the guanine nucleotide releasing
factor, SOS. The Grb-SOS complex can either bind
directly to phosphotyrosine sites in the receptor
or indirectly through Shc. These protein
interactions bring SOS in close proximity to Ras,
allowing for Ras activation. This subsequently
activates the ERK and JNK signaling pathways
that, in turn, activate transcription factors,
such as c-fos, AP-1, and Elk-1, that promote gene
expression and contribute to cell
proliferation. References Daly, R.J., Take your
partners, please - signal diversification by the
erbB family of receptor tyrosine kinases. Growth
Factors, 16, 255-263 (1999). Wells, A., EGF
receptor. Int. J. Biochem. Cell Biol., 31,
637-643 (1999). Rosette, C., Karin, M.,
Ultraviolet light and osmotic stress activation
of the JNK cascade through multiple growth factor
and cytokine receptors. Science, 274, 1194-1197
1996). Qian, X., et al., N terminus of Sos1 Ras
exchange factor critical roles for the Dbl and
pleckstrin homology domains. Mol. Cell Biol., 18,
771-778 (1998).