Tyrosine Kinases / Adaptors

The epidermal growth factor (EGF) receptor is a 170 kDa transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling, internalization and lysosomal degradation (1,2). Phosphorylation of EGF receptor (EGFR) at Tyr845 in the kinase domain is implicated in stabilizing the activation loop, maintaining the active state enzyme and providing a binding surface for substrate proteins (3,4). c-Src is involved in phosphorylation of EGFR at Tyr845 (5). The SH2 domain of PLCγ binds at phospho-Tyr992, resulting in activation of PLCγ-mediated downstream signaling (6). Phosphorylation of EGFR at Tyr1045 creates a major docking site for c-Cbl, an adaptor protein that leads to receptor ubiquitination and degradation following EGFR activation (7,8). The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and Tyr1173) provides a docking site for the Shc scaffold protein, with both sites involved in MAP kinase signaling activation (2). Phosphorylation of EGFR at specific serine and threonine residues attenuates EGFR kinase activity. EGFR carboxy-terminal residues Ser1046 and Ser1047 are phosphorylated by CaM kinase II; mutation of either of these serines results in upregulated EGFR tyrosine autophosphorylation (10).

1. Hackel, P.O. et al. (1999) Curr Opin Cell Biol 11, 184-9.
2. Zwick, E. et al. (1999) Trends Pharmacol Sci 20, 408-12.
3. Cooper, J.A. and Howell, B. (1993) Cell 73, 1051-4.
4. Hubbard, S.R. et al. (1994) Nature 372, 746-54.
5. Biscardi, J.S. et al. (1999) J Biol Chem 274, 8335-43.
6. Emlet, D.R. et al. (1997) J Biol Chem 272, 4079-86.
7. Levkowitz, G. et al. (1999) Mol Cell 4, 1029-40.
8. Ettenberg, S.A. et al. (1999) Oncogene 18, 1855-66.
9. Rojas, M. et al. (1996) J Biol Chem 271, 27456-61.
10. Feinmesser, R.L. et al. (1999) J Biol Chem 274, 16168-73.

• Iordanov, M. S. et al. (2002) The UV (ribotoxic) stress response of human keratinocytes involves the unexpected uncoupling of the Ras-extracellular signal-regulated kinase signaling cascade from the activated epidermal growth factor receptor. Mol. Cell. Biol. 22, 5380-5394. Applications: Western Blotting
• Wu, W. et al. (2002) Src-dependent phosphorylation of the epidermal growth factor receptor on tyrosine 845 is required for zinc-induced Ras activation. J. Biol. Chem. 277, 24252-24257. Applications: Western Blotting
• Tschumperlin, D. J. et al. (2004) Mechanotransduction through growth-factor shedding into the extracellular space. Nature 429, 83-86. Applications: IHC-P (paraffin) Western Blotting
• Rimoldi, V. et al. (2003) Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localization in caveolin-1 enriched domains. Oncogene 22, 6054-6060. Applications: Western Blotting
• Nishimura, M. et al. (2009) Mol Cell Biol 29, 5529-39. Applications: Western Blotting

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Phospho-EGF Receptor (Tyr1068) Antibody

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