Publikation:

PPM1F controls integrin activity via a conserved phospho-switch

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2020

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The Journal of Cell Biology. Rockefeller University Press. 2020, 219(12), e202001057. ISSN 0021-9525. eISSN 1540-8140. Available under: doi: 10.1083/jcb.202001057

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Control of integrin activity is vital during development and tissue homeostasis, while derailment of integrin function contributes to pathophysiological processes. Phosphorylation of a conserved threonine motif (T788/T789) in the integrin β cytoplasmic domain increases integrin activity. Here, we report that T788/T789 functions as a phospho-switch, which determines the association with either talin and kindlin-2, the major integrin activators, or filaminA, an integrin activity suppressor. A genetic screen identifies the phosphatase PPM1F as the critical enzyme, which selectively and directly dephosphorylates the T788/T789 motif. PPM1F-deficient cell lines show constitutive integrin phosphorylation, exaggerated talin binding, increased integrin activity, and enhanced cell adhesion. These gain-of-function phenotypes are reverted by reexpression of active PPM1F, but not a phosphatase-dead mutant. Disruption of the ppm1f gene in mice results in early embryonic death at day E10.5. Together, PPM1F controls the T788/T789 phospho-switch in the integrin β1 cytoplasmic tail and constitutes a novel target to modulate integrin activity.

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570 Biowissenschaften, Biologie

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ISO 690GRIMM, Tanja M., Nina I. DIERDORF, Karin BETZ, Christoph PAONE, Christof R. HAUCK, 2020. PPM1F controls integrin activity via a conserved phospho-switch. In: The Journal of Cell Biology. Rockefeller University Press. 2020, 219(12), e202001057. ISSN 0021-9525. eISSN 1540-8140. Available under: doi: 10.1083/jcb.202001057
BibTex
@article{Grimm2020-12-07PPM1F-52688,
  year={2020},
  doi={10.1083/jcb.202001057},
  title={PPM1F controls integrin activity via a conserved phospho-switch},
  number={12},
  volume={219},
  issn={0021-9525},
  journal={The Journal of Cell Biology},
  author={Grimm, Tanja M. and Dierdorf, Nina I. and Betz, Karin and Paone, Christoph and Hauck, Christof R.},
  note={Article Number: e202001057}
}
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