PI3K/Akt/mTOR · target hub

CASTOR2

Cytosolic arginine sensor for mTORC1 subunit 2 (CASTOR2)

CASTOR2 is a Nutrient & amino-acid sensing (TSC/Rag/GATOR) on the PI3K/Akt/mTOR axis. Functions as a negative regulator of the TORC1 signaling pathway through the GATOR complex. As part of homodimers or heterodimers with CASTOR1, directly binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1. Does not directly bind arginine, but binding of arginine to … It is indexed under "GATOR / CASTOR / Sestrin (amino-acid & stress sensing, selected)" on our pathway page for antibodies, inhibitors, and assay guidance.

Back to pathway overviewSearch: CASTOR2UniProt (A6NHX0)

Research notes

  • Combine with other genes in the same hub block via genetics or pharmacology to test non-redundant roles of CASTOR2.
  • Annotate PIK3CA/PTEN and upstream RTK–Ras context when reading p-AKT, mTORC1/2, or lipid outputs.
  • Verify antibody clone, phospho-site, and stimulation; include KD/KO or inhibitor controls.

On the pathway hub (sections)

Genetic lesions & expression context (quick reference)

Type / exampleDomain / context (brief)
Expression contextTissue/cell-type–dependent expression
Rare variantsSporadic variants—require functional validation
Pathway couplingCo-occurs with neighboring nodes on the hub

Naming and prevalence vary by cohort and assay—annotate clinically with COSMIC, ClinVar, OncoKB, and datasheets; research context only.

Assay readouts for CASTOR2

  • Amino-acid withdrawal/refeed: Rag nucleotide state and mTORC1 lysosomal recruitment.
  • Rheb/TSC: GTP loading or TSC complex IP.
  • Downstream: p-S6K, p-4E-BP1, ULK1 Ser757 (mTORC1 repression marker).
  • Stress: energy deprivation or CASTOR/sestrin manipulations as relevant.

CASTOR2 experimental notes

Examples below reflect common literature and public resources (e.g., CCLE, DepMap)—validate genotypes, expression, and passage in your own stocks before committing assays.

[1] Cell lines commonly used for CASTOR2 studies (examples)

  • Tool lines: HEK293T, MEFs, HeLa, HEK293, C2C12—screen by CASTOR2 expression and pathway context (CCLE/DepMap).
  • Combine with neighbors (DEPDC5, NPRL2, NPRL3, MIOS) via KD/pharmacology to test non-redundancy.
  • Overexpression/rescue in HEK293T supports mechanism and IP workflows.
  • Isogenic/CRISPR models separate pathway dependency from bypass survival.

[2] Cell samples for CASTOR2 Western blot

  • Whole-cell lysates—optimize RIPA/NP-40 per antibody; phosphatase inhibitors for phospho blots.
  • Stimulation: serum starvation ± insulin/EGF or amino-acid withdrawal/refeed as relevant.
  • Controls: siRNA/shRNA, CRISPR KO, or inhibitors to validate band specificity.
  • Loading: BCA normalization; subcellular fractionation when needed.

[3] Tissue samples for CASTOR2 Western blot

  • Matched tumor/adjacent frozen tissues after pathology review.
  • Mouse GEMM or xenografts—mind species antibody cross-reactivity.
  • Primary cells/PDCs when ethically approved.
  • FFPE needs specialized extraction; frozen tissue preferred for phospho work.

[4] Cell samples for CASTOR2 immunoprecipitation

  • Tagged overexpression: HEK293T FLAG/HA-CASTOR2 for complex capture.
  • Endogenous IP: high-expression lines; often ≥1–5×10⁶ cells per IP.
  • Stimulation: ligand or nutrient treatments enrich interactions—pilot time courses.
  • Controls: isotype IgG, empty vector, KD/KO negatives.

Human tissues and primary cells require ethics/IRB approval; tumors are heterogeneous—record histotype, site, and preservation conditions.

Bypass & related pathways

Models & genetics note

Overexpression vs endogenous CASTOR2 can differ in dosage, splicing, and compartmentation—in organoids/PDX, record passage, matrix, and drug history.

Quick search presets

CASTOR2CASTOR2 antibodyPI3K inhibitormTOR inhibitor

CASTOR2-related antibodies (keyword-biased)

Adds CASTOR2 keyword bias atop the PI3K/Akt/mTOR antibody pool—if sparse, use presets above or global search.

Neighboring targets (same hub)

DEPDC5NPRL2NPRL3MIOSWDR24WDR59SEH1LSEC13

External databases & resources

FAQ

This content supports research reagents and pathway education—not medical advice. Annotate mutations, drug indications, and protocols with authoritative databases, datasheets, and institutional oversight.

Last reviewed: 2026-05-18

Related on this site

See the PI3K/Akt/mTOR hub for neighboring nodes and assay guidance—cross-check MAPK, RTK, metabolism, and autophagy pages as needed.

PI3K/Akt/mTOR·MAPK/ERK·Receptor tyrosine kinase·Metabolism