Essential function of adaptor protein Nck1 in platelet-derived growth factor receptor signaling in human lens epithelial cells

Abstract

Binding of platelet-derived growth factor-BB (PDGF-BB) to its cognate receptor (PDGFR) promotes lens epithelial cell (LEC) proliferation and migration. After cataract surgery, these LEC behaviors have been proposed as an influential cause of posterior capsule opacification (PCO). Stimulated PDFGR undergoes dimerization and tyrosine phosphorylation providing docking sites for a SH2-domain-containing noncatalytic region of tyrosine kinase (Nck). Nck is an adaptor protein acting as a linker of the proximal and downstream signaling events. However, the functions of Nck1 protein in LEC have not been investigated so far. We reported here a crucial role of Nck1 protein in regulating PDGFR-mediated LEC activation using LEC with a silenced expression of Nck1 protein. The knockdown of Nck1 suppressed PDGF-BB-stimulated LEC proliferation and migration and disrupted the cell cycle progression especially G1/S transition. LEC lacking Nck1 protein failed to exhibit actin polymerization and membrane protrusions. The downregulation of Nck1 protein in LEC impaired PDGFR‐induced phosphorylation of intracellular signaling proteins, including Erk1/2, Akt, CREB and ATF1, which resulted in inhibition of LEC responses. Therefore, these data suggest that the loss of Nck1 expression may disturb LEC activation and Nck1 may potentially be a drug target to prevent PCO and lens-related disease.

Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis

“…PDGFbb, a member of the PDGF family, is involved in various physiological processes, such as mitosis, differentiation, chemotaxis and angiogenesis ( Wang et al, 2019 ). Within the eye, PDGFbb promotes the proliferation of LECs, thus acting as a safeguard against cataract development that may result from a decline in LECs ( Li et al, 2019 ; Paensuwan et al, 2022 ). Moreover, previous studies have reported elevated levels of VEGF in cataract patients ( Mitrović et al, 2016 ), which is inconsistent with our findings.…”

Long noncoding RNA LINC00885 upregulates NCK1 to promote cell viability and migration of triple-negative breast cancer cells through sponging miR-654-3p

“…At the molecular level, EMT alters the adhesion, polarity and differentiation of epithelial cells and renders them more prone to migration and invasion [ 10 , 11 , 12 ]. The noncatalytic region of tyrosine kinase 1 (NCK1) is an adaptor protein acting as a linker of the proximal and downstream signaling events that are related to the occurrence and development of a variety of tumors [ 13 , 14 ]. NCK1 upregulation promotes the development of ovarian carcinoma (OC) [ 15 , 16 ], colorectal cancer (CoC) [ 17 ] and cervical squamous cell carcinoma [ 18 ].…”