Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts

Jihyun Jeon; Hyangjin Lee; Haein Park; Jung hyun Lee; Sojoong Choi; Jisun Hwang; Inn Oc Han; Eok Soo Oh

doi:10.1016/j.bbrc.2007.10.134

Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts

Jihyun Jeon
, Hyangjin Lee
, Haein Park
, Jung hyun Lee
, Sojoong Choi
, Jisun Hwang
, Inn Oc Han
, Eok Soo Oh

Department of Life Science

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

7 Scopus citations

Abstract

Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs, via tyrosine phosphorylation at specific residues. We recently reported that FAK Tyr-407 phosphorylation negatively regulates the enzymatic and biological activities of FAK, unlike phosphorylation of other tyrosine residues. In this study, we further investigated the effect of FAK Tyr-407 phosphorylation on cell transformation. We found that FAK Tyr-407 phosphorylation was lower in H-Ras transformed NIH3T3 and K-Ras transformed rat-2 fibroblasts than in the respective untransformed control cells. Consistently, FAK Tyr-407 phosphorylation was decreased in parallel with cell transformation in H-Ras-inducible NIH3T3 cells and increased during trichostatin A-induced detransformation of both K-Ras transformed rat-2 fibroblasts and H-Ras transformed NIH3T3 cells. In addition, overexpression of a phosphorylation-mimicking FAK Tyr-407 mutant inhibited morphological transformation of H-Ras-inducible NIH3T3 cells and inhibited invasion activity and anchorage-independent growth of H-Ras-transformed NIH3T3 cells. Taken together, these data strongly suggest that FAK Tyr-407 phosphorylation negatively regulates transformation of fibroblasts.

Original language	English
Pages (from-to)	1062-1066
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	364
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2007.10.134
State	Published - 28 Dec 2007

Bibliographical note

Funding Information:
This study was supported by a grant of the Molecular and Cellular BioDiscovery Research Program (CBM-01B-2-1 to E.S.O.), and in part by a grant of the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0420070-1 to E.S.O.) and Grant No. R15-2006-020 from the NCRC program of the MOST and the KOSEF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University.

Keywords

Focal adhesion kinase
Signal transduction
Transformation
Tyrosine phosphorylation

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10.1016/j.bbrc.2007.10.134

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@article{06fd1a4e226341b3aa3fa5fb9943df4a,

title = "Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts",

abstract = "Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs, via tyrosine phosphorylation at specific residues. We recently reported that FAK Tyr-407 phosphorylation negatively regulates the enzymatic and biological activities of FAK, unlike phosphorylation of other tyrosine residues. In this study, we further investigated the effect of FAK Tyr-407 phosphorylation on cell transformation. We found that FAK Tyr-407 phosphorylation was lower in H-Ras transformed NIH3T3 and K-Ras transformed rat-2 fibroblasts than in the respective untransformed control cells. Consistently, FAK Tyr-407 phosphorylation was decreased in parallel with cell transformation in H-Ras-inducible NIH3T3 cells and increased during trichostatin A-induced detransformation of both K-Ras transformed rat-2 fibroblasts and H-Ras transformed NIH3T3 cells. In addition, overexpression of a phosphorylation-mimicking FAK Tyr-407 mutant inhibited morphological transformation of H-Ras-inducible NIH3T3 cells and inhibited invasion activity and anchorage-independent growth of H-Ras-transformed NIH3T3 cells. Taken together, these data strongly suggest that FAK Tyr-407 phosphorylation negatively regulates transformation of fibroblasts.",

keywords = "Focal adhesion kinase, Signal transduction, Transformation, Tyrosine phosphorylation",

author = "Jihyun Jeon and Hyangjin Lee and Haein Park and Lee, \{Jung hyun\} and Sojoong Choi and Jisun Hwang and Han, \{Inn Oc\} and Oh, \{Eok Soo\}",

note = "Funding Information: This study was supported by a grant of the Molecular and Cellular BioDiscovery Research Program (CBM-01B-2-1 to E.S.O.), and in part by a grant of the National R\&D Program for Cancer Control, Ministry of Health \& Welfare, Republic of Korea (0420070-1 to E.S.O.) and Grant No. R15-2006-020 from the NCRC program of the MOST and the KOSEF through the Center for Cell Signaling \& Drug Discovery Research at Ewha Womans University.",

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doi = "10.1016/j.bbrc.2007.10.134",

language = "English",

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journal = "Biochemical and Biophysical Research Communications",

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T1 - Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts

AU - Jeon, Jihyun

AU - Lee, Hyangjin

AU - Park, Haein

AU - Lee, Jung hyun

AU - Choi, Sojoong

AU - Hwang, Jisun

AU - Han, Inn Oc

AU - Oh, Eok Soo

N1 - Funding Information: This study was supported by a grant of the Molecular and Cellular BioDiscovery Research Program (CBM-01B-2-1 to E.S.O.), and in part by a grant of the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0420070-1 to E.S.O.) and Grant No. R15-2006-020 from the NCRC program of the MOST and the KOSEF through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University.

PY - 2007/12/28

Y1 - 2007/12/28

N2 - Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs, via tyrosine phosphorylation at specific residues. We recently reported that FAK Tyr-407 phosphorylation negatively regulates the enzymatic and biological activities of FAK, unlike phosphorylation of other tyrosine residues. In this study, we further investigated the effect of FAK Tyr-407 phosphorylation on cell transformation. We found that FAK Tyr-407 phosphorylation was lower in H-Ras transformed NIH3T3 and K-Ras transformed rat-2 fibroblasts than in the respective untransformed control cells. Consistently, FAK Tyr-407 phosphorylation was decreased in parallel with cell transformation in H-Ras-inducible NIH3T3 cells and increased during trichostatin A-induced detransformation of both K-Ras transformed rat-2 fibroblasts and H-Ras transformed NIH3T3 cells. In addition, overexpression of a phosphorylation-mimicking FAK Tyr-407 mutant inhibited morphological transformation of H-Ras-inducible NIH3T3 cells and inhibited invasion activity and anchorage-independent growth of H-Ras-transformed NIH3T3 cells. Taken together, these data strongly suggest that FAK Tyr-407 phosphorylation negatively regulates transformation of fibroblasts.

AB - Focal adhesion kinase (FAK) mediates signal transduction in response to multiple extracellular inputs, via tyrosine phosphorylation at specific residues. We recently reported that FAK Tyr-407 phosphorylation negatively regulates the enzymatic and biological activities of FAK, unlike phosphorylation of other tyrosine residues. In this study, we further investigated the effect of FAK Tyr-407 phosphorylation on cell transformation. We found that FAK Tyr-407 phosphorylation was lower in H-Ras transformed NIH3T3 and K-Ras transformed rat-2 fibroblasts than in the respective untransformed control cells. Consistently, FAK Tyr-407 phosphorylation was decreased in parallel with cell transformation in H-Ras-inducible NIH3T3 cells and increased during trichostatin A-induced detransformation of both K-Ras transformed rat-2 fibroblasts and H-Ras transformed NIH3T3 cells. In addition, overexpression of a phosphorylation-mimicking FAK Tyr-407 mutant inhibited morphological transformation of H-Ras-inducible NIH3T3 cells and inhibited invasion activity and anchorage-independent growth of H-Ras-transformed NIH3T3 cells. Taken together, these data strongly suggest that FAK Tyr-407 phosphorylation negatively regulates transformation of fibroblasts.

KW - Focal adhesion kinase

KW - Signal transduction

KW - Transformation

KW - Tyrosine phosphorylation

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JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

Phosphorylation of focal adhesion kinase at Tyrosine 407 negatively regulates Ras transformation of fibroblasts

Abstract

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Keywords

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