Signal transduction pathways in the mitogenic response to G protein-coupled neuropeptide receptor agonists

J Cell Physiol. 1998 Dec;177(4):507-17. doi: 10.1002/(SICI)1097-4652(199812)177:4<507::AID-JCP2>3.0.CO;2-K.


Neuropeptides, including mammalian bombesin-like peptides, act as potent cellular growth factors and have been implicated in a variety of normal and abnormal processes, including development, inflammation, and malignant transformation. These signaling peptides exert their characteristic effects on cellular processes by binding to specific G protein-coupled receptors (GPCR) on the surface of their target cells. Typically, the binding of a neuropeptide to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the synthesis of lipid-derived second messengers with subsequent activation of protein phosphorylation cascades is an important early response to neuropeptides. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of cellular proteins including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. This tyrosine phosphorylation pathway depends on the integrity of the actin cytoskeleton and requires functional Rho. The purpose of this article is to review recent advances in unraveling the pathways that play a role in transducing mitogenic and migratory responses induced by G protein-coupled neuropeptide receptor agonists.

Publication types

  • Review

MeSH terms

  • Animals
  • Arachidonic Acid / physiology
  • Bombesin / pharmacology
  • Calcium Signaling
  • Calcium-Calmodulin-Dependent Protein Kinases / physiology
  • Cell Adhesion Molecules / physiology
  • Cell Movement
  • Crk-Associated Substrate Protein
  • Cytoskeletal Proteins / physiology
  • Cytoskeleton / physiology
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • GTP-Binding Proteins / physiology*
  • Humans
  • Mitosis / physiology*
  • Neuropeptides / physiology
  • Paxillin
  • Phosphatidylinositols / physiology
  • Phosphoproteins / physiology
  • Phosphorylation
  • Prostaglandins / biosynthesis
  • Protein Kinase C / physiology
  • Protein Processing, Post-Translational
  • Protein-Tyrosine Kinases / physiology
  • Proteins*
  • Receptors, Neuropeptide / physiology*
  • Retinoblastoma-Like Protein p130
  • Ribosomal Protein S6 Kinases / physiology
  • Signal Transduction / physiology*


  • BCAR1 protein, human
  • Cell Adhesion Molecules
  • Crk-Associated Substrate Protein
  • Cytoskeletal Proteins
  • Neuropeptides
  • PXN protein, human
  • Paxillin
  • Phosphatidylinositols
  • Phosphoproteins
  • Prostaglandins
  • Proteins
  • Receptors, Neuropeptide
  • Retinoblastoma-Like Protein p130
  • Arachidonic Acid
  • protein kinase D
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Ribosomal Protein S6 Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • GTP-Binding Proteins
  • Bombesin