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

doi:10.1016/j.cellsig.2007.04.002

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

31 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 language	English
Pages (from-to)	1784-1796
Number of pages	13
Journal	Cellular Signalling
Volume	19
Issue number	8
DOIs	https://doi.org/10.1016/j.cellsig.2007.04.002
State	Published - 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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10.1016/j.cellsig.2007.04.002

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@article{17a22c2fc0d64f5484736bcb5f6e1335,

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

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.",

keywords = "Adhesion, Integrin, Migration, Paxillin, Phospholipase C-γ1, Pyk2, Rac1",

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

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.",

year = "2007",

month = aug,

doi = "10.1016/j.cellsig.2007.04.002",

language = "English",

volume = "19",

pages = "1784--1796",

journal = "Cellular Signalling",

issn = "0898-6568",

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T1 - Phospholipase C-γ1 potentiates integrin-dependent cell spreading and migration through Pyk2/paxillin activation

AU - Choi, Jang Hyun

AU - Yang, Yong Ryoul

AU - Lee, Seul Ki

AU - Kim, Il Shin

AU - Ha, Sang Hoon

AU - Kim, Eung Kyun

AU - Bae, Yun Soo

AU - Ryu, Sung Ho

AU - Suh, Pann Ghill

N1 - 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.

PY - 2007/8

Y1 - 2007/8

N2 - 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.

AB - 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.

KW - Adhesion

KW - Integrin

KW - Migration

KW - Paxillin

KW - Phospholipase C-γ1

KW - Pyk2

KW - Rac1

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DO - 10.1016/j.cellsig.2007.04.002

M3 - Article

C2 - 17531443

AN - SCOPUS:34250639027

SN - 0898-6568

VL - 19

SP - 1784

EP - 1796

JO - Cellular Signalling

JF - Cellular Signalling

IS - 8

ER -

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

Abstract

Bibliographical note

Keywords

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