Abstract
βig‐h3 is an extracellular matrix (ECM) protein whose expression is highly induced by transforming growth factor beta1 (TGF‐β1). We previously demonstrated that βig‐h3 has two α3β1 integrin‐interacting motifs, which promote adhesion, migration, and proliferation of human keratinocytes. Both βig‐h3 and TGF‐β1 have been suggested to play important roles in the healing of skin wounds. In this study, we demonstrate that TGF‐β1 enhances keratinocyte adhesion and migration toward βig‐h3 through the α3β1 integrin. TGF‐β1 did not increase the amount of the α3β1 integrin on the cell surface, but rather increased its affinity for βig‐h3. LY294002, an inhibitor of PI3K, blocked the basal and TGF‐β1‐enhanced cell migration but not adhesion to βig‐h3. A constitutively active mutant of PI3K stimulated cell migration but not adhesion to βig‐h3. The PI3K pathway is also not associated with the affinity of the α3β1 integrin to βig‐h3. TGF‐β1 induced phosphorylation of AKT and FAK. Taken together, these data suggest that TGF‐β1 increases affinity of the α3β1 integrin to βig‐h3, resulting in enhanced adhesion and migration of keratinocytes toward βig‐h3. TGF‐β1 also enhances migration through PI3K, but PI3K is not associated with either the binding affinity of the α3β1 integrin or its adhesion to βig‐h3. © 2004 Wiley‐Liss, Inc.