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http://dx.doi.org/10.5352/JLS.2007.17.2.185

Direct tyrosine phosphorylation of Akt/PKB by epidermal growth factor receptor  

Bae, Sun-Sik (Department of Pharmacology and MRC for Ischemic Tissue Regeneration, Pusan National University School Medicine)
Choi, Jang-Hyun (Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology)
Yun, Sung-Ji (Department of Pharmacology and MRC for Ischemic Tissue Regeneration, Pusan National University School Medicine)
Kim, Eun-Kyung (Department of Pharmacology and MRC for Ischemic Tissue Regeneration, Pusan National University School Medicine)
Oh, Yong-Suk (Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology)
Kim, Chi-Dae (Department of Pharmacology and MRC for Ischemic Tissue Regeneration, Pusan National University School Medicine)
Suh, Pann-Ghill (Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology)
Publication Information
Journal of Life Science / v.17, no.2, 2007 , pp. 185-191 More about this Journal
Abstract
Akt/PKB plays pivotal roles in many physiological responses such as proliferation, differentiation, apoptosis, and angiogenesis. Here we show that tyrosine phosphorylation of Akt/PKB is essential for the subsequent phosphorylation at $Thr^{\308}$. Tyrosine phosphorylation of Akt/PKB was induced by stimulation of COS-7 cells with epidermal growth factor receptor (EGF) and its phosphorylation was significantly enhanced by constitutive targeting of Akt/PKB to the plasma membrane by myristoylation. Interestingly, incubation of affinity purified Myc-tagged Akt/PKB with purified EGF receptor resulted in tyrosine phosphorylation as well as $Ser^{\473}$ phosphorylation of Akt/PKB. In addition, tyrosine-phosphorylated Akt/PKB could directly associate with activated EGF receptor in vitro. Finally, alanine mutation at putative tyrosine phosphorylation site $(Tyr^{\326})$ abolished EGF induced $Thr^{\308}$ phosphorylation of wild type as well as constitutively active form of Akt/PKB. Given these results we suggest here that direct tyrosine phosphorylation of Akt/PKB by EGF receptor could be another mechanism of EGF-induced control of many physiological responses.
Keywords
Akt/PKB; Epidermal growth factor receptor; tyrosine phosphorylation; survival; growth;
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