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P-Rex Rac-GEFs.

Heidi C E Welch1

  • 1Signalling Programme, Babraham Institute, Cambridge CB22 3AT, UK.

Cellular Signalling
|May 2, 2026
PubMed
Summary
This summary is machine-generated.

The P-Rex proteins P-Rex1 and P-Rex2 are crucial regulators of cell signaling, impacting immunity, metabolism, and cancer. Recent advances shed light on their diverse roles and therapeutic potential.

Keywords:
GEFsGTPasesGuanine-nucleotide exchange factorsP-Rex1P-Rex2P-Rex2bPREX1PREX2PREX2ARacRho familySmall G proteins

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • P-Rex1 and P-Rex2 are Dbl-type guanine-nucleotide exchange factors (GEFs) activating Rac small GTPases.
  • They act as coincidence detectors for PI3K and GPCR signaling pathways.
  • P-Rex proteins regulate diverse physiological processes including immunity, metabolism, and neural function.

Purpose of the Study:

  • To review the literature on P-Rex proteins from their discovery to recent advances.
  • To highlight the roles of P-Rex1 and P-Rex2 in various physiological and pathological conditions.
  • To discuss recent progress in understanding P-Rex regulation, inhibition, and GEF-independent functions.

Main Methods:

  • Literature review of P-Rex protein family.
  • Analysis of structural data and inhibitor development.
  • Summary of GEF-activity independent functions.

Main Results:

  • P-Rex proteins are implicated in inflammation, immunity, metabolism, and neurological functions.
  • Deregulated P-Rex1 is linked to fibrotic diseases, asthma, and autism.
  • P-Rex1 and P-Rex2 are deregulated in metabolic diseases and various cancers, influencing tumor growth and metastasis.

Conclusions:

  • P-Rex proteins are critical regulators with diverse roles in health and disease.
  • Recent structural and functional studies have advanced our understanding of P-Rex.
  • P-Rex proteins represent potential therapeutic targets for cancer and metabolic diseases.