HRAS Knockout Jurkat Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from Jurkat T lymphocytes, engineered for disruption of the HRAS gene. This heterogeneous pool carries diverse HRAS loss-of-function mutations, providing a robust model for studying HRAS-dependent pathways without clonal bias. The polyclonal format preserves biological variability and enables broad assessment of HRAS functions in signaling, proliferation, and apoptosis.
The Jurkat host is an immortalized CD4+ T-cell line from an acute T-cell leukemia patient, extensively used to investigate T-cell receptor signaling, activation, and apoptosis. Its well-defined signaling architecture and stable growth make it ideal for genetic manipulation and functional dissection of immune cell biology. HRAS is endogenously expressed in Jurkat cells, where it transmits signals from surface receptors to downstream effectors, making this knockout model highly relevant.
HRAS is a small GTPase that cycles between inactive GDP-bound and active GTP-bound states, acting as a molecular switch downstream of activated receptor tyrosine kinases (EGFR, PDGFR), GPCRs, and the Grb2-SOS complex. Active HRAS engages multiple effectors: it directly interacts with RAF1 to activate the MEK1/2-ERK1/2 cascade, leading to phosphorylation of transcription factors such as ELK1, and with the PI3K p110 subunit to stimulate the AKT-mTOR pathway, promoting survival and growth. Other interactors, including RalGDS and PLC??, diversify signal output. Key transcriptional targets include CCND1 (cyclin D1) and MYC, which drive cell cycle progression. Thus, HRAS functions as a central integrator of mitogenic and survival signals.
In Jurkat T cells, HRAS couples T-cell receptor and cytokine receptor engagement to cellular outcomes including proliferation, survival, and apoptosis. Disruption of HRAS in this polyclonal population attenuates MAPK and PI3K signaling, offering a physiologically relevant loss-of-function system to interrogate HRAS-dependent processes in T lymphocytes. This model is particularly suited for exploring the molecular basis of RASopathies like Costello syndrome and HRAS-driven malignancies such as urothelial carcinoma, salivary gland tumors, and skin squamous cell carcinoma. It also enables investigation of germline and somatic HRAS mutations in an immune-cell context.
The HRAS Knockout Jurkat Polyclonal Cells support diverse applications in signal transduction, cancer biology, and pharmacological research. Typical readouts include Western blotting for ERK1/2 phosphorylation, flow cytometric apoptosis analysis with Annexin V, and CFSE proliferation assays. RT-qPCR can quantify expression changes of downstream targets like CCND1 and MYC. Co-immunoprecipitation of HRAS with RAF1 or PI3K p110 in wild-type cells is validated by knockout controls. Phospho-kinase arrays and drug sensitivity studies using MEK inhibitors (e.g., trametinib) can dissect pathway dependencies and therapeutic responses. This product serves as a powerful tool for functional genomics, inhibitor profiling, and mechanistic studies. For further information, contact Ascent Research.
