Jeong Ha-Won, Kim In-San
Cell and Matrix Biology National Research Laboratory, Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Korea.
J Cell Biochem. 2004 Jul 1;92(4):770-80. doi: 10.1002/jcb.20110.
betaig-h3 is an extracellular matrix (ECM) protein whose expression is highly induced by transforming growth factor beta1 (TGF-beta1). We previously demonstrated that betaig-h3 has two alpha3beta1 integrin-interacting motifs, which promote adhesion, migration, and proliferation of human keratinocytes. Both betaig-h3 and TGF-beta1 have been suggested to play important roles in the healing of skin wounds. In this study, we demonstrate that TGF-beta1 enhances keratinocyte adhesion and migration toward betaig-h3 through the alpha3beta1 integrin. TGF-beta1 did not increase the amount of the alpha3beta1 integrin on the cell surface, but rather increased its affinity for betaig-h3. LY294002, an inhibitor of PI3K, blocked the basal and TGF-beta1-enhanced cell migration but not adhesion to betaig-h3. A constitutively active mutant of PI3K stimulated cell migration but not adhesion to betaig-h3. The PI3K pathway is also not associated with the affinity of the alpha3beta1 integrin to betaig-h3. TGF-beta1 induced phosphorylation of AKT and FAK. Taken together, these data suggest that TGF-beta1 increases affinity of the alpha3beta1 integrin to betaig-h3, resulting in enhanced adhesion and migration of keratinocytes toward betaig-h3. TGF-beta1 also enhances migration through PI3K, but PI3K is not associated with either the binding affinity of the alpha3beta1 integrin or its adhesion to betaig-h3.
βig-h3是一种细胞外基质（ECM）蛋白，其表达受到转化生长因子β1（TGF-β1）的高度诱导。我们之前证明βig-h3有两个与α3β1整合素相互作用的基序，可促进人角质形成细胞的黏附、迁移和增殖。βig-h3和TGF-β1均被认为在皮肤伤口愈合中起重要作用。在本研究中，我们证明TGF-β1通过α3β1整合素增强角质形成细胞对βig-h3的黏附与迁移。TGF-β1并未增加细胞表面α3β1整合素的量，而是增加了其对βig-h3的亲和力。PI3K抑制剂LY294002可阻断基础状态下以及TGF-β1增强的细胞迁移，但不影响对βig-h3的黏附。PI3K的组成型活性突变体可刺激细胞迁移，但不影响对βig-h3的黏附。PI3K信号通路也与α3β1整合素对βig-h3的亲和力无关。TGF-β1诱导AKT和FAK磷酸化。综上所述，这些数据表明TGF-β1增加了α3β1整合素对βig-h3的亲和力，从而导致角质形成细胞对βig-h3的黏附与迁移增强。TGF-β1还通过PI3K增强迁移，但PI3K与α3β1整合素的结合亲和力及其对βig-h3的黏附均无关。
