Functional analysis of the cytoplasmic domain of the integrin a1 subunit in endothelial cells (Blood, 2008, 112:3242-3254)

報告日期: 2008/12/16
報告時間: 15:10/16:00
報告學生: 黃俊豪
講評老師: 江美治

 Functional analysis of the cytoplasmic domain of the integrin a1 subunit in endothelial cells



Speaker : 黃俊豪

Commentator : 江美治老師

Date : 2008/12/16 下午3:10-4:00



Integrins are a large family of heterodimeric cell receptors which consist of a and b subunits, and are involved in both cell-cell and cell-extracellular matrix (ECM) interactions. Integrin a1b1, one major collagen receptors of 24 human integrins, plays important roles in angiogenesis. In a previous study, deletion or blocking integrin a1b1 decreased both VEGF-mediated and tumor-associated angiogenesis. However, the mechanism of integrin a1b1-mediated angiogenesis is poorly understood. The authors generated mutants with the deletion, truncation or point mutation of the integrin a1 subunit C-terminal tail and expressed them in α1-null endothelial cells. They found that Pro1444 and Leu1145 were involved in a1b1-mediated cell proliferation, and Lys1146 was required for cell adhesion, migration and tubulogenesis. They also showed that p38 mitogen-activated protein kinase (MAPK) pathway was correlated with integrin a1b1 dpendent endothelial cell migration, and the p38 MAPK and PI3K/Akt activation was required for tubulogenesis. Integrin a1b1- dependent endothelial cell proliferation is primarily mediated by MEK/ERK pathway. In conclusion, they show that various regions of integrin a1 C-terminal tail play an important role in activation of selective signal pathway that regulates specific endothelial cell function.


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