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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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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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.

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

Abstract

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Keywords

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