Serine phosphorylation of the integrin β4 subunit is necessary for epidermal growth factor receptor-induced hemidesmosome disruption

被引:66
|
作者
Wilhelmsen, Kevin [1 ]
Litjens, Sandy H. M. [1 ]
Kuikman, Ingrid [1 ]
Margadant, Coert [1 ]
van Rheenen, Jacco [1 ]
Sonnenberg, Arnoud [1 ]
机构
[1] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands
关键词
D O I
10.1091/mbc.E07-04-0306
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Hemidesmosomes (HDs) are multiprotein adhesion complexes that promote attachment of epithelial cells to the basement membrane. The binding of alpha 6 beta 4 to plectin plays a central role in their assembly. We have defined three regions on beta 4 that together harbor all the serine and threonine phosphorylation sites and show that three serines (S1356, S1360, and S1364), previously implicated in HD regulation, prevent the interaction of beta 4 with the plectin actin-binding domain when phosphorylated. We have also established that epidermal growth factor receptor activation, which is known to function upstream of HD disassembly, results in the phosphorylation of only one or more of these three residues and the partial disassembly of HDs in keratinocytes. Additionally, we show that S1360 and S1364 of beta 4 are the only residues phosphorylated by PKC and PKA in cells, respectively. Taken together, our studies indicate that multiple kinases act in concert to breakdown the structural integrity of HDs in keratinocytes, which is primarily achieved through the phosphorylation of S1356, S1360, and S1364 on the beta 4 subunit.
引用
收藏
页码:3512 / 3522
页数:11
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