PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration.
It is well established that epidermal growth factor (EGF) induces the cytoskeleton reorganization and cell migration through two major signaling cascades: phospholipase C-gamma1 (PLC-gamma1) and Rho GTPases. However, little is known about the cross talk between PLC-gamma1 and Rho GTPases. Here we showed that PLC-gamma1 forms a complex with Rac1 in response to EGF. This interaction is direct and mediated by PLC-gamma1 Src homology 3 (SH3) domain and Rac1 (106)PNTP(109) motif. This interaction is critical for EGF-induced Rac1 activation in vivo, and PLC-gamma1 SH3 domain is actually a potent and specific Rac1 guanine nucleotide exchange factor in vitro. We have also demonstrated that the interaction between PLC-gamma1 SH3 domain and Rac1 play a significant role in EGF-induced F-actin formation and cell migration. We conclude that PLC-gamma1 and Rac1 coregulate EGF-induced cell cytoskeleton remodeling and cell migration by a direct functional interaction.
Li
Siwei
S
Department of Cell Biology, University of Alberta, Edmonton, Canada.
Wang
Qian
Q
Wang
Yi
Y
Chen
Xinmei
X
Wang
Zhixiang
Z
D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects*; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D018909:src Homology Domains
D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D004815:Epidermal Growth Factor; D051966:Phospholipase C gamma; D020830:rac1 GTP-Binding Protein