Epidermal growth factor receptor (EGF R), a transmembrane glycoprotein, is a member of the ErbB receptor tyrosine kinase family. Upon ligand binding, EGF R undergoes dimerization. Specific tyrosine residues in the cytoplasmic domain are subsequently phosphorylated, and adaptor proteins and enzymes are recruited to transmit signals from EGF R via signaling pathways to the nucleus. This regulates diverse biological functions like cell proliferation, differentiation, migration, and apoptosis (Morandell et al. 2008; Yarden and Sliwkowski 2001).
An important signaling pathway downstream of EGF R is RAS/RAF. The adaptor protein growth factor receptor-bound protein 2 (Grb2) complexes with son of sevenless (SOS) associating with EGF R, either directly or through binding to SHC-transforming protein 1 (SHC1) (Waters et al. 1996). SOS mediates the activation of RAS proteins (Downward 1996). Activated RAS recruits and activates RAF family kinases promoting activation of extracellular signal-regulated kinase (ERK) mediated through mitogen activated protein kinase 1 (MEK). Activated kinases move to the nucleus and regulate transcription factors involved in cell proliferation (Liebmann 2001).
The PI3K/AKT cascade is another important target in EGF R signaling (Stover et al.1995). Activated phosphoinositide 3-kinase (PI3K) phosphorylates and activates protein kinase B (AKT), leading to phosphorylation of mammalian target of rapamycin (mTOR). Subsequent phosphorylation of ribosomal protein S6 kinase beta-1 (P70S6K) promotes protein synthesis.
ErbB family members play an important role in the development and malignancy of various human cancers (Mishra et al. 2017). Kinase mutations and/or overexpression of the receptor can result in deregulation in signaling networks; understanding the precise roles of the EGF R-mediated signaling pathways is crucial for translating these findings into new cancer therapies.
We have compiled key antibodies involved in the EGF R signaling pathway into one handy poster you can download for your reference.
Click the pathway components within the images below to discover the key antibodies that Bio-Rad provides.
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