Adhesion-independent alpha6beta4 integrin clustering is mediated by phosphatidylinositol 3-kinase.
Clustering of cell-surface integrins is known to augment integrin-mediated signal transduction, but mechanisms of integrin clustering are poorly understood. Here we report that adhesion-independent clustering of alpha6beta4 integrin, known to be important in mediating tumor cell motility, is driven by phosphatidylinositol 3-kinase (PI3K) but does not require activation of the PI3K-Akt pathway. We observed clustering of alpha6beta4 in breast carcinoma cells after adhesion-independent cross-linking of the beta4 integrin subunit. Clustering was significantly blocked when cross-linking was performed in the presence of PI3K inhibitors LY294002 and wortmannin. In contrast, no significant inhibition of clustering was observed with protein kinase C inhibitor GF109203X, rapamycin, or heparin. Although alpha6beta4 clustering was blocked by PI3K inhibitors, clustering was not associated with increased PI3K lipid kinase activity or increased phosphorylation of Akt. A novel role for PI3K in alpha6beta4 integrin clustering is proposed.
Gilcrease
Michael Z
MZ
Department of Pathology, M. D. Anderson Cancer Center, Houston, Texas, USA. gilcrease@adanderson.org
Zhou
Xiao
X
Welch
Kristin
K
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
D039161:Integrin alpha6beta4; D019869:Phosphatidylinositol 3-Kinases