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Dephosphorylation of Epidermal Growth Factor Receptor by Protein Tyrosine Phosphatase 1B
Author(s) -
Young Melody W,
Kim Youngjoo
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.645.5
Subject(s) - dephosphorylation , phosphorylation , protein tyrosine phosphatase , epidermal growth factor receptor , tyrosine phosphorylation , microbiology and biotechnology , receptor tyrosine kinase , biology , cancer research , signal transduction , tyrosine kinase , tyrosine , chemistry , phosphatase , biochemistry , receptor
Phosphorylation and dephosphorylation are fundamental regulatory mechanisms in a myriad of proteins. Protein tyrosine phosphatases (PTPs) and their integration with protein tyrosine kinases contribute to an important role in the maintenance of normal cell function. More specifically, the reversible phosphorylation of tyrosine residues in receptor tyrosine kinases provides regulation of cellular signaling. PTP1B, Protein Tyrosine Phosphatase 1B, is one of the most well studied PTPs and has been shown to dephosphorylate epidermal growth factor receptor (EGFR). Its purpose is to downregulate EGFR signaling through dephosphorylation of tyrosine residues. In doing so, PTP1B displays both tumor suppressing and tumor promoting effects dependent on cellular conditions. The detailed molecular mechanism of PTP1B in its dephosphorylation of EGFR has not yet been determined. We hypothesize that regulation of EGFR signaling by wild type PTP1B, established by a specific order of dephosphorylation, is important in maintaining in normal cellular function. We examined EGFR dephosphorylation by PTP1B and observed that there is a specific order of dephosphorylation. Furthermore, K197E PTP1B, found in thyroid cancer, had dramatic decrease in rate of EGFR dephosphorylation as well as change in order of dephosphorylation compared to the wild type PTP1B. Our studies presented here provide evidence of PTP1B's ability to fine tune EGFR signaling pathway, and we plan to deduce interactions between EGFR and PTP1B by continuing this study with individual EGFR peptides. Moreover, this research offer insights in cancer therapeutics since dysregulation of EGFR signaling due to PTP1B mutation would affect normal cellular signaling leading to uncontrollable proliferation and differentiation.Tyrosine Residues Dephosphorylation rate WT PTP1B (sec −1 ) Dephosphorylation rate K197E PTP1B (sec −1 ) Fold DifferenceY992 0.88 ± 0.16 0.042 ± 0.008 21.0 Y1068 0.67 ± 0.046 0.054 ± 0.011 12.4 Y1148 0.60 ± 0.24 0.225 ± 0.0043 2.67 Y1173 2.12 ± 0.63 0.040 ± 0.0083 53Western BlotsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .