A Rac-cGMP signaling pathway. Academic Article uri icon

Overview

abstract

  • The small GTPase Rac and the second messenger cGMP (guanosine 3',5'-cyclic monophosphate) are critical regulators of diverse cell functions. When activated by extracellular signals via membrane signaling receptors, Rac executes its functions through engaging downstream effectors such as p21-activated kinase (PAK), a serine/threonine protein kinase. However, the molecular mechanism by which membrane signaling receptors regulate cGMP levels is not known. Here we have uncovered a signaling pathway linking Rac to the increase of cellular cGMP. We show that Rac uses PAK to directly activate transmembrane guanylyl cyclases (GCs), leading to increased cellular cGMP levels. This Rac/PAK/GC/cGMP pathway is involved in platelet-derived growth factor-induced fibroblast cell migration and lamellipodium formation. Our findings connect two important regulators of cellular physiological functions and provide a general mechanism for diverse receptors to modulate physiological responses through elevating cellular cGMP levels.

publication date

  • January 26, 2007

Research

keywords

  • Cyclic GMP
  • Protein Serine-Threonine Kinases
  • Signal Transduction
  • Up-Regulation
  • rac GTP-Binding Proteins

Identity

PubMed Central ID

  • PMC1965458

Scopus Document Identifier

  • 33846279042

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2006.11.048

PubMed ID

  • 17254971

Additional Document Info

volume

  • 128

issue

  • 2