Phospholipase C-gamma1 potentiates integrin-dependent cell spreading and migration through Pyk2/paxillin activation.
Phospholipase C-gamma1 (PLC-gamma1), which generates two second messengers, namely, inositol-1, 4, 5-trisphosphate and diacylglycerol, is implicated in growth factor-mediated chemotaxis. However, the exact role of PLC-gamma1 in integrin-mediated cell adhesion and migration remains poorly understood. In this study, we demonstrate that PLC-gamma1 is required for actin cytoskeletal organization and cell motility through the regulation of Pyk2 and paxillin activation. After fibronectin stimulation, PLC-gamma1 directly interacted with the cytoplasmic tail of integrin beta1. In PLC-gamma1-silenced cells, integrin-induced Pyk2 and paxillin phosphorylation were significantly reduced and PLC-gamma1 potentiated the integrin-induced Pyk2/paxillin activation in its enzymatic activity-dependent manner. In addition, specific knock-down of PLC-gamma1 resulted in a failure to form focal adhesions dependent on fibronectin stimulation, which appeared to be caused by the suppression of Pyk2 and paxillin phosphorylation. Interestingly, PLC-gamma1 potentiated the activations of Rac, thus integrin-induced lamellipodia formation was up-regulated. Consequently, the strength of cell-substratum interaction and cell motility were profoundly up-regulated by PLC-gamma1. Taken together, these results suggest that PLC-gamma1 is a key player in integrin-mediated cell spreading and motility achieved by the activation of Pyk2/paxillin/Rac signaling.
Choi
Jang Hyun
JH
Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk, 790-784, Republic of Korea.
Yang
Yong-Ryoul
YR
Lee
Seul Ki
SK
Kim
Il-Shin
IS
Ha
Sang Hoon
SH
Kim
Eung-Kyun
EK
Bae
Yun Soo
YS
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D051419:Paxillin / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000302:isolation & purification / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism
D016023:Integrins; D051419:Paxillin; D034741:RNA, Small Interfering; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; D051966:Phospholipase C gamma