Document Type

Peer-Reviewed Article

Publication Date

11-17-2022

Abstract

Integrin adhesion receptors provide links between extracellular ligands and cytoplasmic signaling. Multiple kinases have been found to directly engage with integrin β tails, but the molecular basis for these interactions remain unknown. Here, we assess the interaction between the kinase domain of p21-activated kinase 4 (PAK4) and the cytoplasmic tail of integrin β5. We determine three crystal structures of PAK4-β5 integrin complexes and identify the PAK-binding site. This is a region in the membrane-proximal half of the β5 tail and confirmed by site-directed mutagenesis. The β5 tail engages the kinase substrate-binding groove and positions the non-phosphorylatable integrin residue Glu767 at the phosphoacceptor site. Consistent with this, integrin β5 is poorly phosphorylated by PAK4, and in keeping with its ability to occlude the substrate-binding site, weakly inhibits kinase activity. These findings demonstrate the molecular basis for β5 integrin-PAK4 interactions but suggest modifications in understanding the potential cellular role of this interaction.

Comments

Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s42003-022-04157-3.

At the time this article was researched and written Elizabeth Morse Luoma was affiliated with The Department of Cell Biology, Yale University.

DOI

10.1038/s42003-022-04157-3

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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