KMID : 0620920080400030261
|
|
Experimental & Molecular Medicine 2008 Volume.40 No. 3 p.261 ~ p.270
|
|
CD98 activation increases surface expression and clustering of ¥â1 integrins in MCF-7 cells through FAK/Src- and cytoskeleton-independent mechanisms
|
|
Kim Sun-Mi
Hahn Jang-Hee
|
|
Abstract
|
|
|
CD98, a disulfide-linked 125-kDa heterodimeric type II transmembrane glycoprotein, regulates ¥â1 integrinmediated cell adhesion. However, the molecular mechanisms underlying CD98-mediated activation of ¥â1 integrin are presently unclear. In this study, the effects of CD98 signaling on the expression and clustering of ¥â1 integrin were investigated. Activation of CD98 augmented surface expression of ¥â1 integrin on MCF-7 cells. Cross-linking CD98 induced clustering of ¥â1 integrins. Inhibition of phosphorylation of focal adhesion kimase (FAK) by PP2, an inhibitor of Src family kinase, reduced cell-extracellular matrix adhesion, but not surface expression and clustering of ¥â1 integrin on MCF-7 cells. This result was confirmed by over-expression of dominant negative forms of FAK. In addition, phalloidin or cytochalasin D inhibited CD98-mediated induction of cell-ECM adhesion, but not surface expression and clustering of ¥â1 integrins. The inhibitory effects of PP2, cytochalasin D or phalloidin on CD98-stimulated cell adhesion were diminished by pretreatment of cells with Mn2+, which is shown to induce conformational change of integrins. These results provide the first evidence that CD98 activation increases not only ¥â1 integrin affinity but also its surface expression and clustering and the latter is independent of FAK/Src and cytoskeleton.
|
|
KEYWORD
|
|
actins, antigens, CD98, cytoskeleton, focal adhesion kinase, integrin ¥â1
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|