An inhibitory role for FAK in regulating proliferation: A link between limited adhesion and RhoA-ROCK signaling

Dana M. Pirone, Wendy F. Liu, Sami Alom Ruiz, Lin Gao, Srivatsan Raghavan, Christopher A. Lemmon, Lewis Romer, Christopher S. Chen

Research output: Contribution to journalArticle

Abstract

Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK-/- cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK-/- cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression-induced growth, loss of growth control in FAK-/- or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalJournal of Cell Biology
Volume174
Issue number2
DOIs
StatePublished - Jul 17 2006

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Focal Adhesion Protein-Tyrosine Kinases
Growth
Focal Adhesions
Cell Adhesion
Extracellular Matrix
Phosphotransferases
Endothelial Cells
Cell Proliferation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Pirone, D. M., Liu, W. F., Ruiz, S. A., Gao, L., Raghavan, S., Lemmon, C. A., ... Chen, C. S. (2006). An inhibitory role for FAK in regulating proliferation: A link between limited adhesion and RhoA-ROCK signaling. Journal of Cell Biology, 174(2), 277-288. https://doi.org/10.1083/jcb.200510062

An inhibitory role for FAK in regulating proliferation : A link between limited adhesion and RhoA-ROCK signaling. / Pirone, Dana M.; Liu, Wendy F.; Ruiz, Sami Alom; Gao, Lin; Raghavan, Srivatsan; Lemmon, Christopher A.; Romer, Lewis; Chen, Christopher S.

In: Journal of Cell Biology, Vol. 174, No. 2, 17.07.2006, p. 277-288.

Research output: Contribution to journalArticle

Pirone, Dana M. ; Liu, Wendy F. ; Ruiz, Sami Alom ; Gao, Lin ; Raghavan, Srivatsan ; Lemmon, Christopher A. ; Romer, Lewis ; Chen, Christopher S. / An inhibitory role for FAK in regulating proliferation : A link between limited adhesion and RhoA-ROCK signaling. In: Journal of Cell Biology. 2006 ; Vol. 174, No. 2. pp. 277-288.
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