Related Experiment Video

Updated: Jun 10, 2026

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the

Minghao Sun1, Petra Hillmann, Bianca T Hofmann

  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 18, 2010
PubMed

Insights

Cancer mutations in p85alpha (PI3K regulatory subunit) enhance cell growth and PI3K signaling. These p85alpha mutants specifically activate the p110alpha catalytic subunit, driving oncogenic transformation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The phosphatidylinositide 3-kinase (PI3K) pathway is crucial for cell growth and survival.
  • Aberrant PI3K signaling is implicated in various cancers.
  • p85alpha is the regulatory subunit of PI3K, controlling its activity.

Purpose of the Study:

  • To investigate the functional consequences of cancer-specific mutations in p85alpha.
  • To determine the role of specific PI3K isoforms in p85alpha-mediated oncogenesis.

Main Methods:

  • Analysis of p85alpha mutants in cellular transformation assays.
  • Quantitative assessment of oncogenic activity.
  • Use of isoform-specific PI3K inhibitors.

Main Results:

  • Cancer-associated mutations in p85alpha's iSH2 and nSH2 domains confer gain-of-function activity.
  • Mutant p85alpha proteins induce oncogenic transformation, proliferation, and PI3K signaling.
  • p110alpha is identified as the exclusive mediator of p85alpha mutant-induced oncogenic transformation.

Conclusions:

  • Mutations in p85alpha disrupt its inhibitory interaction with p110alpha, leading to constitutive PI3K pathway activation.
  • p110alpha activation by mutant p85alpha is a key driver of cancer development.
  • Targeting the p85alpha-p110alpha interaction may offer therapeutic strategies for PI3K-driven cancers.

More Related Videos

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...