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Cited by 27Cell Adhesion Molecules ResearchProtein Kinase Regulation and GTPase SignalingProtein Tyrosine Phosphatases

PPM1F controls integrin activity via a conserved phospho-switch

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Grimm, Tanja M., Dierdorf, Nina I., Betz, Karin, Paone, Christoph, Hauck, Christof R.·2020·Journal of Cell Biology
DOI 10.1083/jcb.202001057PMC PMC7604772
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Abstract

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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Cited by

Sorted by citations

Authors
Grimm, T. M., Dierdorf, N. I., Betz, K., Paone, C., & Hauck, C. R.
Affiliations
University of Konstanz (DE)
Corresponding author
Hauck, Christof R.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2020-10-29
Volume
219
Issue
12
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.202001057
PMC
PMC7604772
OpenAlex
W3095492905
Cited by
27
References
1
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 6
FWCI
3.51
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • KOPS (University of Konstanz) (submittedVersion, cc-by-nc-sa)
Funders
  • Konstanz Research School Chemical Biology
  • Deutsche Forschungsgemeinschaft (CRC969 project B06)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
beta1 integrin, integrin activation, threonine phosphorylation, dephosphorylation, talin, Kindlin-2, integrin cytoplasmic domain, cell adhesion, embryonic lethality, phosphatase
MeSH terms
Animals, Cell Line, Humans, Membrane Proteins, Neoplasm Proteins, Phosphoprotein Phosphatases, Integrin beta1, Amino Acid Motifs, Mice, Filamins

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