Glycine-extended gastrin stimulates cell proliferation and migration through a Rho- and ROCK-dependent pathway, not a...

Area of Science:

• Gastroenterology
• Cell Biology
• Molecular Signaling

Background:

• Gastrin peptides, including amidated gastrin (Gamide) and glycine-extended gastrin (Ggly), promote gastrointestinal cell growth and movement.
• Gamide signaling involves the cholecystokinin-2 receptor and Rho family GTPases (Rho, Rac, Cdc42), impacting cell proliferation and survival.
• The specific signaling pathways for Ggly-induced cell proliferation and migration remain largely uncharacterized.

Purpose of the Study:

• To investigate the roles of Rho, Rac, and Cdc42 small GTP-binding proteins in mediating Ggly-induced proliferation and migration in mouse gastric epithelial cells (IMGE-5).

Main Methods:

• Utilized the mouse gastric epithelial cell line IMGE-5.
• Assessed Ggly-induced activation of Rho, Rac, and Cdc42.
• Examined the effects of inhibiting Rho (using C3) and ROCK (using Y-27632) on Ggly-stimulated proliferation and migration.
• Investigated the impact of dominant-negative mutants of Rac and Cdc42 on Ggly effects.
• Monitored tyrosine phosphorylation of focal adhesion kinase (FAK).

Main Results:

• Ggly significantly activated Rho and its effector ROCK in IMGE-5 cells.
• Inhibition of Rho or ROCK completely abolished Ggly-stimulated cell proliferation and migration.
• Ggly-induced tyrosine phosphorylation of FAK was observed and reversed by C3 and Y-27632.
• Blocking Rac or Cdc42 pathways with dominant-negative mutants did not impede Ggly-induced proliferation or migration.

Conclusions:

• Ggly stimulates IMGE-5 cell proliferation and migration through a signaling pathway dependent on Rho and ROCK activation.
• The Rac and Cdc42 pathways are not involved in Ggly-mediated IMGE-5 cell proliferation and migration.
• These findings elucidate a specific molecular mechanism for Ggly action in gastric epithelial cells.