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Related Concept Videos

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Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Related Experiment Video

Updated: May 12, 2026

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
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Published on: September 20, 2011

A Rac-cGMP signaling pathway.

Dagang Guo1, Ying-cai Tan, Dawei Wang

  • 1Department of Physiology, Cornell University Weill Medical College, New York, NY 10021, and Division of Experimental Hematology, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA.

Cell
|January 27, 2007
PubMed
Summary

Small GTPase Rac and cyclic GMP (cGMP) are key cell regulators. This study reveals Rac uses PAK to activate guanylyl cyclases, increasing cGMP for cell migration and lamellipodium formation.

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Area of Science:

  • Cellular signaling pathways
  • Molecular mechanisms of cell regulation
  • Biochemistry of second messengers

Background:

  • Small GTPase Rac and cyclic GMP (cGMP) are crucial for cell functions.
  • Rac signaling typically involves p21-activated kinase (PAK) as a downstream effector.
  • The mechanism linking membrane receptors to cGMP regulation remains unclear.

Purpose of the Study:

  • To uncover the signaling pathway connecting Rac to cellular cGMP increase.
  • To elucidate how Rac influences cGMP levels via its effectors.
  • To understand the role of this pathway in cell migration and morphology.

Main Methods:

  • Investigated Rac-PAK interactions and their effect on guanylyl cyclase (GC) activity.
  • Utilized cell-based assays to measure cGMP levels.
  • Examined the role of the Rac/PAK/GC/cGMP pathway in fibroblast cell migration and lamellipodium formation.

Main Results:

  • Demonstrated that Rac, via PAK, directly activates transmembrane guanylyl cyclases (GCs).
  • Showed this activation leads to elevated intracellular cGMP levels.
  • Confirmed the Rac/PAK/GC/cGMP pathway's involvement in platelet-derived growth factor-induced fibroblast cell migration and lamellipodium formation.

Conclusions:

  • Established a novel signaling pathway linking Rac to cGMP production through PAK and GCs.
  • Connected Rac and cGMP signaling, two critical regulators of cellular physiology.
  • Provided a general mechanism for receptor-mediated modulation of physiological responses via cGMP elevation.