Fig. 3: PIPn signaling in IFs regulating cell growth and motility.
From: Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics
This figure illustrates the pivotal role of PIPn signaling in regulating cell proliferation and migration through its interaction with IFs. Activation of cell-surface receptors triggers the production of PIPns (e.g., PtdIns4P, PtdIns(4,5)P2, PtdIns(3,4,5)P3), leading to AKT activation. This activation prompts AKT to phosphorylate PKP1, causing it to disengage from desmosomal IFs and diminishing cell adhesion. The phosphorylated PKP1 then interacts with 14-3-3γ, which fosters cell proliferation and migration. The stimulation of S6K and inhibition of 4E-BP by mTORC1-mediated phosphorylation downstream of the PI3K/AKT signaling pathway promote protein synthesis by influencing the eIF4 complex. The phosphorylation of PKP1 enhances eIF4 activity, which relaxes the complex structures in the 5’-UTR of mRNA, leading to increased protein production and cell growth. Within the nucleus, Lamin A/C interacts with PtdIns(4,5)P2, likely generated through the sequential actions of nuclear class I PITPα/β, PI4KIIα, and PIPKIα. The binding of PtdIns(4,5)P2 promotes the phosphorylation of Lamin A/C, leading to the formation of a complex with NM1. This complex activates RNA polymerase II (Pol II) transcription, thereby driving cell proliferation. This diagram is generated using BioRender.
