Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion - PubMed (original) (raw)

. 2001 Jun 1;276(22):19512-23.

doi: 10.1074/jbc.M009063200. Epub 2001 Feb 21.

Affiliations

• PMID: 11278462
• DOI: 10.1074/jbc.M009063200

Free article

Focal adhesion kinase activates Stat1 in integrin-mediated cell migration and adhesion

B Xie et al. J Biol Chem. 2001.

Free article

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 (FAKDeltaC14) 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.

PubMed Disclaimer

Similar articles

• Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain.
  Chen R, Kim O, Li M, Xiong X, Guan JL, Kung HJ, Chen H, Shimizu Y, Qiu Y. Chen R, et al. Nat Cell Biol. 2001 May;3(5):439-44. doi: 10.1038/35074500. Nat Cell Biol. 2001. PMID: 11331870
• Association of Grb7 with phosphoinositides and its role in the regulation of cell migration.
  Shen TL, Han DC, Guan JL. Shen TL, et al. J Biol Chem. 2002 Aug 9;277(32):29069-77. doi: 10.1074/jbc.M203085200. Epub 2002 May 20. J Biol Chem. 2002. PMID: 12021278
• PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation.
  Kadaré G, Toutant M, Formstecher E, Corvol JC, Carnaud M, Boutterin MC, Girault JA. Kadaré G, et al. J Biol Chem. 2003 Nov 28;278(48):47434-40. doi: 10.1074/jbc.M308562200. Epub 2003 Sep 18. J Biol Chem. 2003. PMID: 14500712
• Role of focal adhesion kinase in integrin signaling.
  Guan JL. Guan JL. Int J Biochem Cell Biol. 1997 Aug-Sep;29(8-9):1085-96. doi: 10.1016/s1357-2725(97)00051-4. Int J Biochem Cell Biol. 1997. PMID: 9416004 Review.
• Control of motile and invasive cell phenotypes by focal adhesion kinase.
  Schlaepfer DD, Mitra SK, Ilic D. Schlaepfer DD, et al. Biochim Biophys Acta. 2004 Jul 5;1692(2-3):77-102. doi: 10.1016/j.bbamcr.2004.04.008. Biochim Biophys Acta. 2004. PMID: 15246681 Review.

Cited by

• {beta}1 Integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation.
  Defilippi P, Rosso A, Dentelli P, Calvi C, Garbarino G, Tarone G, Pegoraro L, Brizzi MF. Defilippi P, et al. J Cell Biol. 2005 Mar 28;168(7):1099-108. doi: 10.1083/jcb.200405116. J Cell Biol. 2005. PMID: 15795318 Free PMC article.
• The role of STATs in lung carcinogenesis: an emerging target for novel therapeutics.
  Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. Karamouzis MV, et al. J Mol Med (Berl). 2007 May;85(5):427-36. doi: 10.1007/s00109-006-0152-3. Epub 2007 Jan 10. J Mol Med (Berl). 2007. PMID: 17216202 Review.
• The interferon-β/STAT1 axis drives the collective invasion of skin squamous cell carcinoma with sealed intercellular spaces.
  Kumagai Y, Nio-Kobayashi J, Ishihara S, Enomoto A, Akiyama M, Ichihara R, Haga H. Kumagai Y, et al. Oncogenesis. 2022 May 24;11(1):27. doi: 10.1038/s41389-022-00403-9. Oncogenesis. 2022. PMID: 35606369 Free PMC article.
• Roles of interleukin-6 in activation of STAT proteins and recruitment of neutrophils during Escherichia coli pneumonia.
  Jones MR, Quinton LJ, Simms BT, Lupa MM, Kogan MS, Mizgerd JP. Jones MR, et al. J Infect Dis. 2006 Feb 1;193(3):360-9. doi: 10.1086/499312. Epub 2005 Dec 27. J Infect Dis. 2006. PMID: 16388483 Free PMC article.
• Promyelocytic leukemia protein (PML) regulates endothelial cell network formation and migration in response to tumor necrosis factor α (TNFα) and interferon α (IFNα).
  Cheng X, Liu Y, Chu H, Kao HY. Cheng X, et al. J Biol Chem. 2012 Jul 6;287(28):23356-67. doi: 10.1074/jbc.M112.340505. Epub 2012 May 15. J Biol Chem. 2012. PMID: 22589541 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Molecular Biology Databases

  • GlyGen glycoinformatics resource

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal