Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion

Bing Xie, Jihe Zhao, Motoo Kitagawa, Joan Durbin, Joseph A. Madri, Jun Lin Guan, Xin Yuan Fu

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Recent studies suggest that focal adhesion kinase (FAK) is important for cell migration. We now suggest a mechanism by which FAK activates the signal transducer and activator of transcription (STAT) pathway, regulating cell adhesion and migration. In particular, we observe that FAK is capable of activating Stat1, but not Stat3. Co-immunoprecipitation and in vitro binding assays demonstrate that Stat1 is transiently and directly associated with FAK during cell adhesion, and Stat1 is activated in this process. FAK with a C-terminal deletion (FAKΔC14) completely abolishes this interaction, indicating this association is dependent on the C-terminal domain of FAK, which is required for FAK localization at focal contacts. Moreover, Stat1 activation during cell adhesion is diminished in FAK-deficient cells, correlating with decreased migration in these cells. Finally, we show that depletion of Stat1 results in an enhancement of cell adhesion and a decrease in cell migration. Thus, our results have demonstrated, for the first time, a critical signaling pathway from integrin/FAK to Stat1 that reduces cell adhesion and promotes cell migration.

Original languageEnglish (US)
Pages (from-to)19512-19523
Number of pages12
JournalJournal of Biological Chemistry
Volume276
Issue number22
DOIs
StatePublished - Jun 1 2001
Externally publishedYes

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
Cell Adhesion
Integrins
Cell Movement
Adhesion
Cell adhesion
Focal Adhesions
Critical Pathways
Transcription
Transducers
Immunoprecipitation
Assays
Chemical activation
Association reactions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Xie, B., Zhao, J., Kitagawa, M., Durbin, J., Madri, J. A., Guan, J. L., & Fu, X. Y. (2001). Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion. Journal of Biological Chemistry, 276(22), 19512-19523. https://doi.org/10.1074/jbc.M009063200

Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion. / Xie, Bing; Zhao, Jihe; Kitagawa, Motoo; Durbin, Joan; Madri, Joseph A.; Guan, Jun Lin; Fu, Xin Yuan.

In: Journal of Biological Chemistry, Vol. 276, No. 22, 01.06.2001, p. 19512-19523.

Research output: Contribution to journalArticle

Xie, B, Zhao, J, Kitagawa, M, Durbin, J, Madri, JA, Guan, JL & Fu, XY 2001, 'Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion', Journal of Biological Chemistry, vol. 276, no. 22, pp. 19512-19523. https://doi.org/10.1074/jbc.M009063200
Xie, Bing ; Zhao, Jihe ; Kitagawa, Motoo ; Durbin, Joan ; Madri, Joseph A. ; Guan, Jun Lin ; Fu, Xin Yuan. / Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 22. pp. 19512-19523.
@article{826a30f438b04dbb80b6ac80d9631079,
title = "Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion",
abstract = "Recent studies suggest that focal adhesion kinase (FAK) is important for cell migration. We now suggest a mechanism by which FAK activates the signal transducer and activator of transcription (STAT) pathway, regulating cell adhesion and migration. In particular, we observe that FAK is capable of activating Stat1, but not Stat3. Co-immunoprecipitation and in vitro binding assays demonstrate that Stat1 is transiently and directly associated with FAK during cell adhesion, and Stat1 is activated in this process. FAK with a C-terminal deletion (FAKΔC14) completely abolishes this interaction, indicating this association is dependent on the C-terminal domain of FAK, which is required for FAK localization at focal contacts. Moreover, Stat1 activation during cell adhesion is diminished in FAK-deficient cells, correlating with decreased migration in these cells. Finally, we show that depletion of Stat1 results in an enhancement of cell adhesion and a decrease in cell migration. Thus, our results have demonstrated, for the first time, a critical signaling pathway from integrin/FAK to Stat1 that reduces cell adhesion and promotes cell migration.",
author = "Bing Xie and Jihe Zhao and Motoo Kitagawa and Joan Durbin and Madri, {Joseph A.} and Guan, {Jun Lin} and Fu, {Xin Yuan}",
year = "2001",
month = "6",
day = "1",
doi = "10.1074/jbc.M009063200",
language = "English (US)",
volume = "276",
pages = "19512--19523",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "22",

}

TY - JOUR

T1 - Focal Adhesion Kinase Activates Stat1 in Integrin-mediated Cell Migration and Adhesion

AU - Xie, Bing

AU - Zhao, Jihe

AU - Kitagawa, Motoo

AU - Durbin, Joan

AU - Madri, Joseph A.

AU - Guan, Jun Lin

AU - Fu, Xin Yuan

PY - 2001/6/1

Y1 - 2001/6/1

N2 - Recent studies suggest that focal adhesion kinase (FAK) is important for cell migration. We now suggest a mechanism by which FAK activates the signal transducer and activator of transcription (STAT) pathway, regulating cell adhesion and migration. In particular, we observe that FAK is capable of activating Stat1, but not Stat3. Co-immunoprecipitation and in vitro binding assays demonstrate that Stat1 is transiently and directly associated with FAK during cell adhesion, and Stat1 is activated in this process. FAK with a C-terminal deletion (FAKΔC14) completely abolishes this interaction, indicating this association is dependent on the C-terminal domain of FAK, which is required for FAK localization at focal contacts. Moreover, Stat1 activation during cell adhesion is diminished in FAK-deficient cells, correlating with decreased migration in these cells. Finally, we show that depletion of Stat1 results in an enhancement of cell adhesion and a decrease in cell migration. Thus, our results have demonstrated, for the first time, a critical signaling pathway from integrin/FAK to Stat1 that reduces cell adhesion and promotes cell migration.

AB - Recent studies suggest that focal adhesion kinase (FAK) is important for cell migration. We now suggest a mechanism by which FAK activates the signal transducer and activator of transcription (STAT) pathway, regulating cell adhesion and migration. In particular, we observe that FAK is capable of activating Stat1, but not Stat3. Co-immunoprecipitation and in vitro binding assays demonstrate that Stat1 is transiently and directly associated with FAK during cell adhesion, and Stat1 is activated in this process. FAK with a C-terminal deletion (FAKΔC14) completely abolishes this interaction, indicating this association is dependent on the C-terminal domain of FAK, which is required for FAK localization at focal contacts. Moreover, Stat1 activation during cell adhesion is diminished in FAK-deficient cells, correlating with decreased migration in these cells. Finally, we show that depletion of Stat1 results in an enhancement of cell adhesion and a decrease in cell migration. Thus, our results have demonstrated, for the first time, a critical signaling pathway from integrin/FAK to Stat1 that reduces cell adhesion and promotes cell migration.

UR - http://www.scopus.com/inward/record.url?scp=0035378669&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035378669&partnerID=8YFLogxK

U2 - 10.1074/jbc.M009063200

DO - 10.1074/jbc.M009063200

M3 - Article

VL - 276

SP - 19512

EP - 19523

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 22

ER -