Protein kinases C-gamma and -delta are involved in insulin-like growth factor I-induced migration of colonic epithelial cells.
OBJECTIVE
The mechanisms by which epithelial cells migrate during the repair of damaged colonic mucosa are poorly understood. This study investigated the insulin-like growth factor I (IGF-I) signaling pathway leading to HT29-D4 human colonic epithelial cell line migration.


METHODS
IGF-stimulated cell migration was determined using a wound model in the presence or absence of kinase inhibitors. Activation of protein kinase C (PKC) was determined by immunodetection.


RESULTS
IGF-I and insulin induce cell migration without affecting cell proliferation through their cognate receptors. Des(1-3)-IGF-I, a truncated analogue of IGF-I, was more potent than IGF-I, suggesting that IGF-binding proteins secreted in the medium modulated IGF-I-induced cell migration. Inhibition of phosphatidylinositol 3-kinase, PKC, and mitogen-activated protein kinases eliminated cell restitution. Long-term exposure of cells to phorbol myristate acetate caused the depletion of PKC-delta and -gamma and prevented also IGF-I-induced cell motility. IGF-I also induced activation of PKC-delta and -gamma only.


CONCLUSIONS
IGF-I stimulates colonic restitution through the activation of multiple signaling pathways including activation of phosphatidylinositol 3-kinase, PKC-delta and -gamma, and mitogen-activated protein kinases.
André
F
F
ESA CNRS 6032, Laboratoire de Biochimie Cellulaire, Universités d'Aix-Marseille I et II, Faculté de Pharmacie, Marseille, France.
Rigot
V
V
Remacle-Bonnet
M
M
Luis
J
J
Pommier
G
G
Marvaldi
J
J
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000166:cytology* / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051745:Protein Kinase C-delta
D007328:Insulin; D018976:Insulin-Like Growth Factor Binding Protein 6; D007527:Isoenzymes; D010446:Peptide Fragments; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; C087857:protein kinase C gamma; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D017871:Calcium-Calmodulin-Dependent Protein Kinases