IQGAP1 activates Tcf signal independent of Rac1 and Cdc42 in injury and repair of bronchial epithelial cells.
The process of injury and repair involves spreading, migration and cell proliferation. The functions of Rho GTPases and their effector IQGAP1 are poor known in this process of airway epithelium. In the present study, we employed a widely used in vitro model by scratching a monolayer of BECs. We found that scratching induced decreasing of the GTP-bound Rac1 and Cdc42, but increasing the amounts of IQGAP1 at different time points. Next, we confirmed that IQGAP1 interacted with the constitutively active Rac1 (Rac1(V12)) and Cdc42 (Cdc42(V12)) rather than the dominant negative Rac1 (Rac1(N17)) and Cdc42 (Cdc42(N17)). Over-expressions of wild type (WT) IQGAP1 and its mutant (T1050AX2), which was defective to interact with Rho GTPases, induced translocation of beta-catenin from the cytoplasm into the nucleus. These results activated Tcf/Lef and increased the expression levels of its target genes of c-myc and cyclin D1. Likewise, the amounts of c-myc and cyclin D1 increased after scratching. Our results suggested that IQGAP1 mediated cell proliferation through activating Tcf in a manner independent of Rac1 and Cdc42 in wound repair of BECs.
Wang
Yongping
Y
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Wang
Aifeng
A
Wang
Fang
F
Wang
Mangxiang
M
Zhu
Min
M
Ma
Yan
Y
Wu
Renliang
R
D000818:Animals; D001980:Bronchi / Q000201:enzymology / Q000473:pathology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology*; D013552:Swine; D051820:TCF Transcription Factors / Q000378:metabolism; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
C101203:IQ motif containing GTPase activating protein 1; D051820:TCF Transcription Factors; D020703:ras GTPase-Activating Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein