Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes

Min A. Oh; Suyong Choi; Mi Ji Lee; Moon Chang Choi; Sin Ae Lee; Wonil Ko; William G. Cance; Eok Soo Oh; Laszlo Buday; Sung Hoon Kim; Jung Weon Lee

doi:10.1016/j.bbamcr.2009.01.015

Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes

Min A. Oh, Suyong Choi, Mi Ji Lee, Moon Chang Choi, Sin Ae Lee, Wonil Ko, William G. Cance, Eok Soo Oh, Laszlo Buday, Sung Hoon Kim, Jung Weon Lee

Department of Life Science

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

9 Scopus citations

Abstract

Cell adhesion to the extracellular matrix (ECM) can activate signaling via focal adhesion kinase (FAK) leading to dynamic regulation of cellular morphology. Mechanistic basis for the lack of effective intracellular signaling by non-attached epithelial cells is poorly understood. To examine whether signaling in suspended cells is regulated by Fer cytoplasmic tyrosine kinase, we investigated the effect of ectopic Fer expression on signaling in suspended or adherent hepatocytes. We found that ectopic Fer expression in Huh7 hepatocytes in suspension or on non-permissive poly-lysine caused significant phosphorylation of FAK Tyr577, Tyr861, or Tyr925, but not Tyr397 or Tyr576. Fer-mediated FAK phosphorylation in suspended cells was independent of c-Src activity or growth factor stimulation, but dependent of cortactin expression. Consistent with these results, complex formation between FAK, Fer, and cortactin was observed in suspended cells. The Fer-mediated effect correlated with multiple membrane protrusions, even on poly-lysine. Together, these observations suggest that Fer may allow a bypass of anchorage-dependency for intracellular signal transduction in hepatocytes.

Original language	English
Pages (from-to)	781-791
Number of pages	11
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1793
Issue number	5
DOIs	https://doi.org/10.1016/j.bbamcr.2009.01.015
State	Published - May 2009

Bibliographical note

Funding Information:
This work was supported by the grant funded by the Korea government [Research Programs for CPMRC, R13-2007-019-00000-0 from Korea Ministry of Education, Science and Technology to S-H Kim, New Drug Target Discovery, 2007-03536, and Cell Dynamic Research Center, R11-2007-007-01004-0 to J.W. Lee] and in part by research grant from Cancer Research Institute, Seoul National University (2007, to J.W. Lee).

Keywords

Cell adhesion
Cortactin
Fer
Focal adhesion kinase
Protein-protein interaction

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10.1016/j.bbamcr.2009.01.015

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Oh, M. A., Choi, S., Lee, M. J., Choi, M. C., Lee, S. A., Ko, W., Cance, W. G., Oh, E. S., Buday, L., Kim, S. H., & Lee, J. W. (2009). Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes. Biochimica et Biophysica Acta - Molecular Cell Research, 1793(5), 781-791. https://doi.org/10.1016/j.bbamcr.2009.01.015

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title = "Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes",

abstract = "Cell adhesion to the extracellular matrix (ECM) can activate signaling via focal adhesion kinase (FAK) leading to dynamic regulation of cellular morphology. Mechanistic basis for the lack of effective intracellular signaling by non-attached epithelial cells is poorly understood. To examine whether signaling in suspended cells is regulated by Fer cytoplasmic tyrosine kinase, we investigated the effect of ectopic Fer expression on signaling in suspended or adherent hepatocytes. We found that ectopic Fer expression in Huh7 hepatocytes in suspension or on non-permissive poly-lysine caused significant phosphorylation of FAK Tyr577, Tyr861, or Tyr925, but not Tyr397 or Tyr576. Fer-mediated FAK phosphorylation in suspended cells was independent of c-Src activity or growth factor stimulation, but dependent of cortactin expression. Consistent with these results, complex formation between FAK, Fer, and cortactin was observed in suspended cells. The Fer-mediated effect correlated with multiple membrane protrusions, even on poly-lysine. Together, these observations suggest that Fer may allow a bypass of anchorage-dependency for intracellular signal transduction in hepatocytes.",

keywords = "Cell adhesion, Cortactin, Fer, Focal adhesion kinase, Protein-protein interaction",

author = "Oh, {Min A.} and Suyong Choi and Lee, {Mi Ji} and Choi, {Moon Chang} and Lee, {Sin Ae} and Wonil Ko and Cance, {William G.} and Oh, {Eok Soo} and Laszlo Buday and Kim, {Sung Hoon} and Lee, {Jung Weon}",

note = "Funding Information: This work was supported by the grant funded by the Korea government [Research Programs for CPMRC, R13-2007-019-00000-0 from Korea Ministry of Education, Science and Technology to S-H Kim, New Drug Target Discovery, 2007-03536, and Cell Dynamic Research Center, R11-2007-007-01004-0 to J.W. Lee] and in part by research grant from Cancer Research Institute, Seoul National University (2007, to J.W. Lee).",

year = "2009",

month = may,

doi = "10.1016/j.bbamcr.2009.01.015",

language = "English",

volume = "1793",

pages = "781--791",

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AU - Oh, Min A.

AU - Choi, Suyong

AU - Lee, Mi Ji

AU - Choi, Moon Chang

AU - Lee, Sin Ae

AU - Ko, Wonil

AU - Cance, William G.

AU - Oh, Eok Soo

AU - Buday, Laszlo

AU - Kim, Sung Hoon

AU - Lee, Jung Weon

N1 - Funding Information: This work was supported by the grant funded by the Korea government [Research Programs for CPMRC, R13-2007-019-00000-0 from Korea Ministry of Education, Science and Technology to S-H Kim, New Drug Target Discovery, 2007-03536, and Cell Dynamic Research Center, R11-2007-007-01004-0 to J.W. Lee] and in part by research grant from Cancer Research Institute, Seoul National University (2007, to J.W. Lee).

PY - 2009/5

Y1 - 2009/5

N2 - Cell adhesion to the extracellular matrix (ECM) can activate signaling via focal adhesion kinase (FAK) leading to dynamic regulation of cellular morphology. Mechanistic basis for the lack of effective intracellular signaling by non-attached epithelial cells is poorly understood. To examine whether signaling in suspended cells is regulated by Fer cytoplasmic tyrosine kinase, we investigated the effect of ectopic Fer expression on signaling in suspended or adherent hepatocytes. We found that ectopic Fer expression in Huh7 hepatocytes in suspension or on non-permissive poly-lysine caused significant phosphorylation of FAK Tyr577, Tyr861, or Tyr925, but not Tyr397 or Tyr576. Fer-mediated FAK phosphorylation in suspended cells was independent of c-Src activity or growth factor stimulation, but dependent of cortactin expression. Consistent with these results, complex formation between FAK, Fer, and cortactin was observed in suspended cells. The Fer-mediated effect correlated with multiple membrane protrusions, even on poly-lysine. Together, these observations suggest that Fer may allow a bypass of anchorage-dependency for intracellular signal transduction in hepatocytes.

AB - Cell adhesion to the extracellular matrix (ECM) can activate signaling via focal adhesion kinase (FAK) leading to dynamic regulation of cellular morphology. Mechanistic basis for the lack of effective intracellular signaling by non-attached epithelial cells is poorly understood. To examine whether signaling in suspended cells is regulated by Fer cytoplasmic tyrosine kinase, we investigated the effect of ectopic Fer expression on signaling in suspended or adherent hepatocytes. We found that ectopic Fer expression in Huh7 hepatocytes in suspension or on non-permissive poly-lysine caused significant phosphorylation of FAK Tyr577, Tyr861, or Tyr925, but not Tyr397 or Tyr576. Fer-mediated FAK phosphorylation in suspended cells was independent of c-Src activity or growth factor stimulation, but dependent of cortactin expression. Consistent with these results, complex formation between FAK, Fer, and cortactin was observed in suspended cells. The Fer-mediated effect correlated with multiple membrane protrusions, even on poly-lysine. Together, these observations suggest that Fer may allow a bypass of anchorage-dependency for intracellular signal transduction in hepatocytes.

KW - Cell adhesion

KW - Cortactin

KW - Fer

KW - Focal adhesion kinase

KW - Protein-protein interaction

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U2 - 10.1016/j.bbamcr.2009.01.015

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AN - SCOPUS:67349177014

SN - 0167-4889

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EP - 791

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 5

ER -

Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes

Abstract

Bibliographical note

Keywords

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