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Title: Glycine-extended gastrin stimulates cell proliferation and migration through a Rho- and ROCK-dependent pathway, not a Rac/Cdc42-dependent pathway.
Austin Authors: He, Hong ;Pannequin, Julie;Tantiongco, John-Paul;Shulkes, Arthur;Baldwin, Graham S
Affiliation: Dept. of Surgery, Univ. of Melbourne, Austin Health, Studley Rd., Heidelberg, Victoria 3084, Australia
Issue Date: 21-Apr-2005
Publication information: American Journal of Physiology. Gastrointestinal and Liver Physiology 2005; 289(3): G478-88
Abstract: Both amidated gastrin (Gamide) and glycine-extended gastrin (Ggly) stimulate gastrointestinal cell proliferation and migration. Binding of Gamide to the cholecystokinin-2 receptor activates small GTP-binding proteins of the Rho family (Rho, Rac, and Cdc42), and dominant-negative mutants of Rho or Cdc42 block Gamide-stimulated cell proliferation and survival. In comparison, little is known about the Ggly signaling transduction pathway leading to cell proliferation and migration. The present study examined the roles of the small G proteins Rho, Rac, and Cdc42 in Ggly-induced proliferation and migration of the mouse gastric epithelial cell line IMGE-5. Ggly stimulated the activation of Rho and its downstream effector protein ROCK. The activation of Rho and ROCK mediated Ggly-induced cell proliferation and migration as inhibition of Rho by C3, or ROCK by Y-27632, completely blocked these effects of Ggly. Ggly also stimulated tyrosine phosphorylation of focal adhesion kinase, and stimulation was reversed by addition of C3 and Y-27632. In contrast to the effects of Rho and ROCK, inhibition of the Rac or Cdc42 pathways by expression of dominant-negative mutants of Rac or Cdc42 did not affect Ggly-induced cell proliferation and migration. These results demonstrate that Ggly stimulates IMGE-5 cell proliferation and migration through a Rho/ROCK-dependent pathway but not via Rac- or Cdc42-dependent pathways.
Gov't Doc #: 15845872
DOI: 10.1152/ajpgi.00034.2005
Journal: American journal of physiology. Gastrointestinal and liver physiology
Type: Journal Article
Subjects: Animals
Cell Culture Techniques
Cell Movement
Cell Proliferation
Gastric Mucosa.cytology
Gastrointestinal Tract.cytology.physiology
Intracellular Signaling Peptides and Proteins
Protein-Serine-Threonine Kinases.physiology
Signal Transduction
rac GTP-Binding Proteins.physiology
rho GTP-Binding Proteins.physiology
rho-Associated Kinases
Appears in Collections:Journal articles

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