Interaction of integrin alpha(6)beta(4) with ErbB3 and implication in heregulin-induced ErbB3/ErbB2-mediated DNA synthesis.
Integrin alpha(6)beta(4) is abundantly expressed in normal epithelial cells and forms hemidesmosomes, one of cell-extracellular matrix junctions. In many types of cancer cells, integrin alpha(6)beta(4) is up-regulated, laminin, an integrin alpha(6)beta(4)-binding extracellular matrix protein, is cleaved, and hemidesmosomes are disrupted, eventually causing an enhancement of cancer cell movement and a facilitation of their invasion. It was previously shown that integrin alpha(6)beta(4) interacts with ErbB1 and ErbB2 and enhances cell proliferation and motility. Here we show that integrin alpha(6)beta(4) interacts with ErbB3 but not with ErbB1, ErbB2 or ErbB4, and enhances the heregulin-induced, ErbB3/ErbB2 heterodimer-mediated DNA synthesis, but not cell motility, in A549 cells.
Kawano
Satoshi
S
Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan.
Mizutani
Kiyohito
K
Miyata
Muneaki
M
Ikeda
Wataru
W
Takai
Yoshimi
Y
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis* / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism*; D020890:Neuregulin-1 / Q000494:pharmacology*; D011485:Protein Binding; D055503:Protein Multimerization / Q000187:drug effects; D034622:RNA Interference; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D004247:DNA; D039161:Integrin alpha6beta4; D020890:Neuregulin-1; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3