The DVL2 Knockout K-562 Polyclonal Cells product provides a pool of CRISPR/Cas9-edited K-562 human chronic myelogenous leukemia (CML) cells carrying targeted disruption of the DVL2 gene. This polyclonal knockout cell population is designed for loss-of-function studies of Dishevelled 2 (DVL2), a central scaffold protein in Wnt signal transduction.
K-562 is a suspension cell line with lymphoblast morphology derived from the pleural effusion of a 53-year-old female with CML in blast crisis. It is widely used as a model for myeloid leukemia and hematopoietic cell biology, offering a tractable system for studying oncogenic signaling, differentiation, and drug responses.
DVL2 functions as a cytoplasmic phosphoprotein that transduces signals from Frizzled (FZD) receptors, acting as a key hub in both canonical (??-catenin-dependent) and non-canonical (PCP and Wnt/Ca2+) pathways. Upon Wnt ligand binding, DVL2 is recruited to the membrane where it interacts with FZD, LRP5/6, and the ??-catenin destruction complex components AXIN1, APC, CK1??, and GSK-3??. This recruitment leads to inhibition of ??-catenin phosphorylation and subsequent stabilization of ??-catenin, which translocates to the nucleus and forms complexes with TCF/LEF transcription factors to activate target genes such as AXIN2, c-MYC, CCND1, and MMP7. In parallel, DVL2 activates non-canonical signaling through RHO/JNK-mediated cytoskeletal rearrangements and calcium flux via PLC, interacting with VANGL1/2, PRICKLE, CELSR, and PAR polarity proteins. DVL2 activity is modulated by upstream kinases CK1 and GSK-3?? and by negative regulators such as DACT1 and PP2A.
In K-562 cells, Wnt signaling contributes to hematopoietic stem cell self-renewal and leukemogenesis, and DVL2 overexpression has been implicated in various malignancies including leukemia, breast cancer, and colorectal cancer. Disruption of DVL2 in this CML background provides a suitable model to dissect Wnt-dependent proliferative and migratory signals, to investigate cross-talk between canonical and non-canonical pathways, and to screen for modulators of DVL2-mediated oncogenic networks.
This polyclonal knockout cell pool is applicable to a range of experimental strategies including functional genomics screens, validation of downstream targets by RT-qPCR and western blotting, TopFlash reporter assays for ??-catenin-mediated transcription, co-immunoprecipitation to map DVL2 interaction networks, phospho-signaling analysis, migration assays, and drug sensitivity profiling. Researchers can employ these cells to interrogate Wnt pathway regulation in a hematopoietic context, to identify synthetic lethal interactions, or to evaluate therapeutic candidates targeting Wnt-driven leukemias. For further details, please contact Ascent Research.
