| First Author | Grimm TM | Year | 2020 |
| Journal | J Cell Biol | Volume | 219 |
| Issue | 12 | PubMed ID | 33119040 |
| Mgi Jnum | J:305499 | Mgi Id | MGI:6705831 |
| Doi | 10.1083/jcb.202001057 | Citation | Grimm TM, et al. (2020) PPM1F controls integrin activity via a conserved phospho-switch. J Cell Biol 219(12) |
| abstractText | 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 beta 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 beta1 cytoplasmic tail and constitutes a novel target to modulate integrin activity. |
