| α-Parvin belongs to the parvin family of adaptor proteins within the IPP (ILK/PINCH/parvin) complex that bridges integrin extracellular matrix receptors to the actin cytoskeleton at focal adhesions. α-parvin organizes two calponin-homology domains that bind F-actin alongside a paxillin-binding CH2 subdomain and ankyrin repeats that engage ILK and PINCH for ternary complex assembly at integrin tails. Upon ECM engagement, ERK-mediated N-terminal serine phosphorylation dissociates α-parvin from TESK1 cofilin kinase, relieving inhibition to enable cofilin phosphorylation, LIMK1 activation, and F-actin stabilization at lamellipodia for directional motility. α-parvin simultaneously recruits CdGAP to hydrolyze Rac1-GTP, tempering lamellipodial expansion while promoting focal adhesion turnover through paxillin-LIMK signaling that balances protrusion with traction force generation. Interaction with α-actinin cross-links actin filaments to ILK pseudokinase activity, propagating FAK/Src cascades that phosphorylate paxillin for RIPLET-mediated ubiquitination and endocytic recycling of integrin clusters during migration. α-parvin coordinates epithelial sheet migration and myofibroblast contractility in wound healing, with ubiquitous expression adapting to mechanical cues via stiffness-dependent ILK conformational shifts. During mitosis, cyclin B1-CDK1 phosphorylation modulates α-parvin localization to the spindle, linking cytoskeletal reorganization to chromosome segregation fidelity. Dysregulation elevates α-parvin in invasive carcinomas, where hyperphosphorylation sustains Rac1 hyperactivation and matrix metalloproteinase secretion for basement membrane breaching. |
Lane 1: Hela, Lane 2: COS-7, Lane 3: NIH/3T3, Lane 4: C6
