ArticleThe Journal of cell biology2020
PPM1F controls integrin activity via a conserved phospho-switch.
Article in The Journal of cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- The phosphatase PPM1F, a negative regulator of integrin activity, is essential for embryonic development and controls tumor cell invasion.BMC biology · 2025Article
- The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus.Journal of neurochemistry · 2025Article
- Leucine rich repeat containing 15 promotes triple-negative breast cancer proliferation and invasion via the ITGB1/FAK/PI3K signalling pathway.Scientific reports · 2025Article
- PPM1F regulates ovarian cancer progression by affecting the dephosphorylation of ITGB1.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Integrin alpha L: structure, cellular functions, and emerging role in human diseases.Frontiers in immunology · 2025Review
- A flexible loop in the paxillin LIM3 domain mediates its direct binding to integrin β subunits.PLoS biology · 2024Article
- Cardioprotective Effects of Exercise: The Role of Irisin and Exosome.Current vascular pharmacology · 2024Review
- Regulation of Renin Expression by Β1-Integrin in As4.1 Juxtaglomerular Line Cells.Biomedicines · 2023Article
- Review
- New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain.Life science alliance · 2022Article
- How integrin phosphorylations regulate cell adhesion and signaling.Trends in biochemical sciences · 2022Review
- Elimination of negative feedback in TLR signalling allows rapid and hypersensitive detection of microbial contaminants.Scientific reports · 2021Article
- Article
- Protein phosphatases in TLR signaling.Cell communication and signaling : CCS · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.