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Identification Of A Potential Receptor That Couples Ion Transport To Protein Kinase Activity
Author(s) -
Ye Qiqi,
Li Zhichuan,
Tian Jiang,
Xie Jeffrey X,
Liu Lijun,
Xie Zijian
Publication year - 2011
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.25.1_supplement.932.8
Subject(s) - proto oncogene tyrosine protein kinase src , chemistry , kinase , ouabain , atpase , microbiology and biotechnology , ion transporter , biophysics , biochemistry , enzyme , biology , sodium , membrane , organic chemistry
In our previous studies, we have demonstrated that the Src‐coupled α1 Na/K‐ATPase works as a receptor for cardiotonic steroids, such as ouabain, to regulate cellular protein kinase cascades. Here, we further explore the structural determinants of the interaction between the α1 Na/K‐ATPase and Src, and demonstrate that the Src‐coupled α1 Na/K‐ATPase allows the cell to decode the transmembrane transport activity of the Na/K‐ATPase to turn on/off protein kinases. The α1 Na/K‐ATPase undergoes E1/E2 conformational transition during an ion pumping cycle. The amount of E1 and E2 Na/K‐ATPase is regulated by extracellular K + and intracellular Na + . Using purified enzyme preparations we find that the E1 Na/K‐ATPase can bind both the Src SH2 and kinase domains simultaneously, and keep Src in an inactive state. Conversely, the E1 to E2 transition releases the kinase domain and activates the associated Src. Moreover, we demonstrate that changes in E1/E2 Na/K‐ATPase by either Na + or K + are capable of regulating Src and Src effectors in live cells. Together, the data suggest that the Src‐coupled α1 Na/K‐ATPase act as a Na + /K + receptor, allowing salt to regulate cellular function through protein kinases.