Int. J. Mol. Sci. 2013, 14(6), 10761-10790; doi:10.3390/ijms140610761
Review

Cellular Functions Regulated by Phosphorylation of EGFR on Tyr845

Received: 28 February 2013; in revised form: 6 May 2013 / Accepted: 13 May 2013 / Published: 23 May 2013
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: The Src gene product (Src) and the epidermal growth factor receptor (EGFR) are prototypes of oncogene products and function primarily as a cytoplasmic non-receptor tyrosine kinase and a transmembrane receptor tyrosine kinase, respectively. The identification of Src and EGFR, and the subsequent extensive investigations of these proteins have long provided cutting edge research in cancer and other molecular and cellular biological studies. In 1995, we reported that the human epidermoid carcinoma cells, A431, contain a small fraction of Src and EGFR in which these two kinase were in physical association with each other, and that Src phosphorylates EGFR on tyrosine 845 (Y845) in the Src-EGFR complex. Y845 of EGFR is located in the activation segment of the kinase domain, where many protein kinases contain kinase-activating autophosphorylation sites (e.g., cAMP-dependent protein kinase, Src family kinases, transmembrane receptor type tyrosine kinases) or trans-phosphorylation sites (e.g., cyclin-dependent protein kinase, mitogen-activated protein kinase, Akt protein kinase). A number of studies have demonstrated that Y845 phosphorylation serves an important role in cancer as well as normal cells. Here we compile the experimental facts involving Src phosphorylation of EGFR on Y845, by which cell proliferation, cell cycle control, mitochondrial regulation of cell metabolism, gamete activation and other cellular functions are regulated. We also discuss the physiological relevance, as well as structural insights of the Y845 phosphorylation.
Keywords: apoptosis; cancer; cell proliferation; EGF; mitochondria; phosphorylation; signal transduction; Src
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MDPI and ACS Style

Sato, K.-I. Cellular Functions Regulated by Phosphorylation of EGFR on Tyr845. Int. J. Mol. Sci. 2013, 14, 10761-10790.

AMA Style

Sato K-I. Cellular Functions Regulated by Phosphorylation of EGFR on Tyr845. International Journal of Molecular Sciences. 2013; 14(6):10761-10790.

Chicago/Turabian Style

Sato, Ken-ichi. 2013. "Cellular Functions Regulated by Phosphorylation of EGFR on Tyr845." Int. J. Mol. Sci. 14, no. 6: 10761-10790.

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