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Cited by 358

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Binding of Src to Na+/K+-ATPase Forms a Functional Signaling Complex

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Tian, Jiang, Cai, Ting, Yuan, Zhaokan, Wang, Haojie, Liu, Lijun, Haas, Michael, Maksimova, Elena, Huang, Xin-Yun, Xie, Zi-Jian·2006·Molecular Biology of the Cell

Abstract

We have shown that ouabain activates Src, resulting in subsequent tyrosine phosphorylation of multiple effectors. Here, we tested if the Na+/K+-ATPase and Src can form a functional signaling complex. In LLC-PK1 cells the Na+/K+-ATPase and Src colocalized in the plasma membrane. Fluorescence resonance energy transfer analysis indicated that both proteins were in close proximity, suggesting a direct interaction. GST pulldown assay showed a direct, ouabain-regulated, and multifocal interaction between the α1 subunit of Na+/K+-ATPase and Src. Although the interaction between the Src kinase domain and the third cytosolic domain (CD3) of α1 is regulated by ouabain, the Src SH3SH2 domain binds to the second cytosolic domain constitutively. Functionally, binding of Src to either the Na+/K+-ATPase or GST-CD3 inhibited Src activity. Addition of ouabain, but not vanadate, to the purified Na+/K+-ATPase/Src complex freed the kinase domain and restored the Src activity. Consistently, exposure of intact cells to ouabain apparently increased the distance between the Na+/K+-ATPase and Src. Concomitantly, it also stimulated tyrosine phosphorylation of the proteins that are associated with the Na+/K+-ATPase. These new findings illustrate a novel molecular mechanism of signal transduction involving the interaction of a P-type ATPase and a nonreceptor tyrosine kinase.

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Metadata

Authors
Tian, J., Cai, T., Yuan, Z., Wang, H., Liu, L., Haas, M., Maksimova, E., Huang, X.-Y., & Xie, Z.-J.
Venue
Molecular Biology of the Cell
Published
2006-01
Volume
17
Issue
1
Pages
317-326
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2101313549
Cited by
358
References
37
FWCI
6.34
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Binding of Src to Na+/K+-ATPase Forms a Functional Signaling Complex. https://app.cochat.ai/papers/10.1091/mbc.e05-08-0735
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Tian, J., Cai, T., Yuan, Z., Wang, H., Liu, L., Haas, M., Maksimova, E., Huang, X.-Y., & Xie, Z.-J. (2006). Binding of Src to Na+/K+-ATPase Forms a Functional Signaling Complex. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.e05-08-0735

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