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Cell signalling

Moving forward in reverse

Nature Reviews Molecular Cell Biology volume 2, page 719 (2001)Cite this article

The authors started with a two-hybrid screen to identify proteins that interact with the cytoplasmic domain of ephrin-B1 in a phosphotyrosine-dependent manner. All the resulting 19 clones encoded an adaptor protein called Grb4 (also known as Nck-2 and Nckβ), which contains one Src-homology-2 (SH2) domain, essential for the interaction with ephrin-B1, and three SH3 domains. The authors used glutathione-S-transferase pull-down experiments and co-immunoprecipitation to verify this interaction in mammalian cells, and then visualized the recruitment of Grb4 to ephrin-B1 in live cells.

What is the effect of this interaction? Cowan and Henkemeyer examined the cytoskeleton after ephrin-B1 reverse signalling, and found a marked loss of polymerized actin. Not only that, but cells rounded up and shrank, as though adhesive contacts had been lost, and the focal adhesion marker paxillin was seen to re-distribute from the plasma membrane to the cytoplasm. Finally, catalytic activity of focal adhesion kinase (FAK) was found to increase.

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ORIGINAL RESEARCH PAPER

  1. Cowan, C. A. & Henkemeyer, M. The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals. Nature 413, 174–179 (2001)

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  1. Alison Mitchell
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Mitchell, A. Moving forward in reverse. Nat Rev Mol Cell Biol 2, 719 (2001). https://doi.org/10.1038/35096051

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