Phospholipase C-γ1 potentiates integrin-dependent cell spreading and migration through Pyk2/paxillin activation

Jang Hyun Choi, Yong Ryoul Yang, Seul Ki Lee, Il Shin Kim, Sang Hoon Ha, Eung Kyun Kim, Yun Soo Bae, Sung Ho Ryu, Pann Ghill Suh

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Phospholipase C-γ1 (PLC-γ1), 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-γ1 in integrin-mediated cell adhesion and migration remains poorly understood. In this study, we demonstrate that PLC-γ1 is required for actin cytoskeletal organization and cell motility through the regulation of Pyk2 and paxillin activation. After fibronectin stimulation, PLC-γ1 directly interacted with the cytoplasmic tail of integrin β1. In PLC-γ1-silenced cells, integrin-induced Pyk2 and paxillin phosphorylation were significantly reduced and PLC-γ1 potentiated the integrin-induced Pyk2/paxillin activation in its enzymatic activity-dependent manner. In addition, specific knock-down of PLC-γ1 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-γ1 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-γ1. Taken together, these results suggest that PLC-γ1 is a key player in integrin-mediated cell spreading and motility achieved by the activation of Pyk2/paxillin/Rac signaling.

Original languageEnglish
Pages (from-to)1784-1796
Number of pages13
JournalCellular Signalling
Volume19
Issue number8
DOIs
StatePublished - Aug 2007

Bibliographical note

Funding Information:
This study was supported by the National R and D Program for Fusion Strategy of Advanced Technologies of Ministry of Commerce, Industry and Energy (MOCIE). In addition, this work was supported by the National Research Laboratory of the Korea Science and Engineering Foundation (grant M10600000281-06J0000-28110) and Brain Korea21 Program of the Ministry of Education of Korea.

Keywords

  • Adhesion
  • Integrin
  • Migration
  • Paxillin
  • Phospholipase C-γ1
  • Pyk2
  • Rac1

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