Related Experiment Video
Updated: Oct 17, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
JAK3-Mediated Structural Remodeling of β-Catenin Suppresses Epithelial-Mesenchymal Transition: Insights from In
Jugal Kishore Das1, Jayshree Mishra1, Narendra Kumar1
1Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA.
Introduction:
Janus kinase 3 (JAK3) is a non-receptor tyrosine kinase that phosphorylates multiple proteins, including β-catenin, a critical component of adherens junctions (AJs). We previously demonstrated that JAK3-mediated phosphorylation of β-catenin regulates its basolateral localization and preserves epithelial barrier integrity. However, the structural basis underlying JAK3-β-catenin interactions and their role in epithelial-mesenchymal transition (EMT) remains unclear.
Methodology:
Here, we employed homology modeling, molecular docking, and structural simulations to investigate phosphorylation-dependent interactions between JAK3 and β-catenin.
Results:
Our analysis revealed that Src-mediated phosphorylation at Y654 induces conformational remodeling of the β-catenin N-terminal domain (NTD), creating a favorable interface for JAK3 binding and shifting its interaction from the armadillo repeat domain to the NTD. Subsequent JAK3-mediated phosphorylation at Y30, Y64, and Y86 restores β-catenin conformation, stabilizes the E-cadherin/β-catenin complex, and limits nuclear translocation. Phosphomimetic analyses identified distinct structural contributions of these residues.
Conclusions:
Collectively, these findings reveal a sequential Src-JAK3 phosphorylation mechanism that maintains AJ integrity and suppresses EMT, providing potential therapeutic insights into epithelial cancer progression.
Related Concept Videos
Catenins
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Cadherins in Tissue Organization
Cell Sorting During Development
Cell sorting plays an...
Tension Response at Adherens Junctions
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
Cell-matrix's Response to Mechanical Forces
Anchoring junctions mechanically attach a cell to the...
TGF - β Signaling Pathway
Cell Motility through Blebbing
Blebbing Through the Matrix
In multicellular...

