PI3K/Akt/mTOR · target hub

PHLPP1

PH domain leucine-rich repeat-containing protein phosphatase 1 (PHLPP1)

PHLPP1 is a PIP₃ / Akt phosphatase or PP2A regulation on the PI3K/Akt/mTOR axis. Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRK… It is indexed under "Akt / mTOR-directed phosphatases & PP2A subunits (selected)" on our pathway page for antibodies, inhibitors, and assay guidance.

Back to pathway overviewSearch: PHLPP1UniProt (O60346)

Research notes

  • Combine with other genes in the same hub block via genetics or pharmacology to test non-redundant roles of PHLPP1.
  • 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 PHLPP1

  • Lipid pools: PIP₃, PI(3,4)P₂, or substrates relevant to PHLPP1.
  • Loss-of-function: CRISPR/siRNA often elevates p-AKT and growth readouts (context-dependent).
  • Tumor specimens: matched tumor/adjacent with mutation/expression annotation.
  • Inhibitor controls: PI3K/mTOR inhibitors to test phenotypic reversibility.

PHLPP1 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 PHLPP1 studies (examples)

  • Tool lines: MCF-7, U87, PC-3, HEK293T, A549—screen by PHLPP1 expression and pathway context (CCLE/DepMap).
  • Combine with neighbors (PHLPP2, PPP2CA, PPP2CB, PPP2R1A) 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 PHLPP1 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 PHLPP1 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 PHLPP1 immunoprecipitation

  • Tagged overexpression: HEK293T FLAG/HA-PHLPP1 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 PHLPP1 can differ in dosage, splicing, and compartmentation—in organoids/PDX, record passage, matrix, and drug history.

Quick search presets

PHLPP1PHLPP1 antibodyPI3K inhibitormTOR inhibitor

PHLPP1-related antibodies (keyword-biased)

Adds PHLPP1 keyword bias atop the PI3K/Akt/mTOR antibody pool—if sparse, use presets above or global search.

Neighboring targets (same hub)

PHLPP2PPP2CAPPP2CBPPP2R1APPP2R1BPPP2R2APPP2R2BPPP2R2C

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