Shoc2-tranduced ERK1/2 motility signals - Novel insights from functional genomics

Myoungkun Jeoung; Eun Ryoung Jang; Jinpeng Liu; Chi Wang; Eric C. Rouchka; Xiaohong Li; Emilia Galperin

doi:10.1016/j.cellsig.2016.02.005

Shoc2-tranduced ERK1/2 motility signals - Novel insights from functional genomics

Myoungkun Jeoung, Eun Ryoung Jang, Jinpeng Liu, Chi Wang, Eric C. Rouchka, Xiaohong Li, Emilia Galperin

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

11 Scopus citations

Abstract

The extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway plays a central role in defining various cellular fates. Scaffold proteins modulating ERK1/2 activity control growth factor signals transduced by the pathway. Here, we analyzed signals transduced by Shoc2, a critical positive modulator of ERK1/2 activity. We found that loss of Shoc2 results in impaired cell motility and delays cell attachment. As ERKs control cellular fates by stimulating transcriptional response, we hypothesized that the mechanisms underlying changes in cell adhesion could be revealed by assessing the changes in transcription of Shoc2-depleted cells. Using quantitative RNA-seq analysis, we identified 853 differentially expressed transcripts. Characterization of the differentially expressed genes showed that Shoc2 regulates the pathway at several levels, including expression of genes controlling cell motility, adhesion, crosstalk with the transforming growth factor beta (TGFβ) pathway, and expression of transcription factors. To understand the mechanisms underlying delayed attachment of cells depleted of Shoc2, changes in expression of the protein of extracellular matrix (lectin galactoside-binding soluble 3-binding protein; LGALS3BP) were functionally analyzed. We demonstrated that delayed adhesion of the Shoc2-depleted cells is a result of attenuated expression and secretion of LGALS3BP. Together our results suggest that Shoc2 regulates cell motility by modulating ERK1/2 signals to cell adhesion.

Original language	English
Pages (from-to)	448-459
Number of pages	12
Journal	Cellular Signalling
Volume	28
Issue number	5
DOIs	https://doi.org/10.1016/j.cellsig.2016.02.005
State	Published - May 1 2016

Bibliographical note

Funding Information:
We thank Drs. Matthew Gentry, Tianyan Gao, Charles Waechter and Stacy Smith for providing reagents and critical reading of the manuscript; the Genetic Technologies Core at the Department of Molecular and Cellular Biochemistry (University of Kentucky) for assistance with the production of lentiviruses; and the UK Flow Cytometry & Cell Sorting core facility for assistance in cell sorting. The Genetic Technologies and Protein cores mentioned above are supported in part by a grant from the National Institute of General Medical Sciences (P20GM103486). The UK Flow Cytometry & Cell Sorting core facility is supported in part by the Office of the Vice President for Research, the Markey Cancer Center and an NCI Center Core Support Grant (P30CA177558) to the University of Kentucky Markey Cancer Center. Bioinformatics support for this work provided by National Institutes of Health (NIH) grants P20GM103436 (Nigel Cooper, PI). This project was supported by grants from the National Cancer Institute (R00CA126161 to EG), the National Institute of General Medical Sciences (P20GM103486) (formally supported by the Center for Research Resources), the National Institute of General Medical Sciences (R01GM113087 to EG) and from the American Cancer Society (RSG-14-172-01-CSM to EG). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS.

Funding Information:
We thank Drs. Matthew Gentry, Tianyan Gao, Charles Waechter and Stacy Smith for providing reagents and critical reading of the manuscript; the Genetic Technologies Core at the Department of Molecular and Cellular Biochemistry (University of Kentucky) for assistance with the production of lentiviruses; and the UK Flow Cytometry & Cell Sorting core facility for assistance in cell sorting. The Genetic Technologies and Protein cores mentioned above are supported in part by a grant from the National Institute of General Medical Sciences ( P20GM103486 ). The UK Flow Cytometry & Cell Sorting core facility is supported in part by the Office of the Vice President for Research , the Markey Cancer Center and an NCI Center Core Support Grant ( P30CA177558 ) to the University of Kentucky Markey Cancer Center. Bioinformatics support for this work provided by National Institutes of Health (NIH) grants P20GM103436 (Nigel Cooper, PI). This project was supported by grants from the National Cancer Institute ( R00CA126161 to EG), the National Institute of General Medical Sciences ( P20GM103486 ) (formally supported by the Center for Research Resources), the National Institute of General Medical Sciences ( R01GM113087 to EG) and from the American Cancer Society ( RSG-14-172-01-CSM to EG). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. Appendix A

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

Adhesion
ERK1/2
LGALS3BP
Motility
Shoc2 scaffold
Transcription

ASJC Scopus subject areas

Cell Biology

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10.1016/j.cellsig.2016.02.005

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title = "Shoc2-tranduced ERK1/2 motility signals - Novel insights from functional genomics",

abstract = "The extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway plays a central role in defining various cellular fates. Scaffold proteins modulating ERK1/2 activity control growth factor signals transduced by the pathway. Here, we analyzed signals transduced by Shoc2, a critical positive modulator of ERK1/2 activity. We found that loss of Shoc2 results in impaired cell motility and delays cell attachment. As ERKs control cellular fates by stimulating transcriptional response, we hypothesized that the mechanisms underlying changes in cell adhesion could be revealed by assessing the changes in transcription of Shoc2-depleted cells. Using quantitative RNA-seq analysis, we identified 853 differentially expressed transcripts. Characterization of the differentially expressed genes showed that Shoc2 regulates the pathway at several levels, including expression of genes controlling cell motility, adhesion, crosstalk with the transforming growth factor beta (TGFβ) pathway, and expression of transcription factors. To understand the mechanisms underlying delayed attachment of cells depleted of Shoc2, changes in expression of the protein of extracellular matrix (lectin galactoside-binding soluble 3-binding protein; LGALS3BP) were functionally analyzed. We demonstrated that delayed adhesion of the Shoc2-depleted cells is a result of attenuated expression and secretion of LGALS3BP. Together our results suggest that Shoc2 regulates cell motility by modulating ERK1/2 signals to cell adhesion.",

keywords = "Adhesion, ERK1/2, LGALS3BP, Motility, Shoc2 scaffold, Transcription",

author = "Myoungkun Jeoung and Jang, {Eun Ryoung} and Jinpeng Liu and Chi Wang and Rouchka, {Eric C.} and Xiaohong Li and Emilia Galperin",

note = "Funding Information: We thank Drs. Matthew Gentry, Tianyan Gao, Charles Waechter and Stacy Smith for providing reagents and critical reading of the manuscript; the Genetic Technologies Core at the Department of Molecular and Cellular Biochemistry (University of Kentucky) for assistance with the production of lentiviruses; and the UK Flow Cytometry & Cell Sorting core facility for assistance in cell sorting. The Genetic Technologies and Protein cores mentioned above are supported in part by a grant from the National Institute of General Medical Sciences (P20GM103486). The UK Flow Cytometry & Cell Sorting core facility is supported in part by the Office of the Vice President for Research, the Markey Cancer Center and an NCI Center Core Support Grant (P30CA177558) to the University of Kentucky Markey Cancer Center. Bioinformatics support for this work provided by National Institutes of Health (NIH) grants P20GM103436 (Nigel Cooper, PI). This project was supported by grants from the National Cancer Institute (R00CA126161 to EG), the National Institute of General Medical Sciences (P20GM103486) (formally supported by the Center for Research Resources), the National Institute of General Medical Sciences (R01GM113087 to EG) and from the American Cancer Society (RSG-14-172-01-CSM to EG). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. Funding Information: We thank Drs. Matthew Gentry, Tianyan Gao, Charles Waechter and Stacy Smith for providing reagents and critical reading of the manuscript; the Genetic Technologies Core at the Department of Molecular and Cellular Biochemistry (University of Kentucky) for assistance with the production of lentiviruses; and the UK Flow Cytometry & Cell Sorting core facility for assistance in cell sorting. The Genetic Technologies and Protein cores mentioned above are supported in part by a grant from the National Institute of General Medical Sciences ( P20GM103486 ). The UK Flow Cytometry & Cell Sorting core facility is supported in part by the Office of the Vice President for Research , the Markey Cancer Center and an NCI Center Core Support Grant ( P30CA177558 ) to the University of Kentucky Markey Cancer Center. Bioinformatics support for this work provided by National Institutes of Health (NIH) grants P20GM103436 (Nigel Cooper, PI). This project was supported by grants from the National Cancer Institute ( R00CA126161 to EG), the National Institute of General Medical Sciences ( P20GM103486 ) (formally supported by the Center for Research Resources), the National Institute of General Medical Sciences ( R01GM113087 to EG) and from the American Cancer Society ( RSG-14-172-01-CSM to EG). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the NIGMS. Appendix A Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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N2 - The extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway plays a central role in defining various cellular fates. Scaffold proteins modulating ERK1/2 activity control growth factor signals transduced by the pathway. Here, we analyzed signals transduced by Shoc2, a critical positive modulator of ERK1/2 activity. We found that loss of Shoc2 results in impaired cell motility and delays cell attachment. As ERKs control cellular fates by stimulating transcriptional response, we hypothesized that the mechanisms underlying changes in cell adhesion could be revealed by assessing the changes in transcription of Shoc2-depleted cells. Using quantitative RNA-seq analysis, we identified 853 differentially expressed transcripts. Characterization of the differentially expressed genes showed that Shoc2 regulates the pathway at several levels, including expression of genes controlling cell motility, adhesion, crosstalk with the transforming growth factor beta (TGFβ) pathway, and expression of transcription factors. To understand the mechanisms underlying delayed attachment of cells depleted of Shoc2, changes in expression of the protein of extracellular matrix (lectin galactoside-binding soluble 3-binding protein; LGALS3BP) were functionally analyzed. We demonstrated that delayed adhesion of the Shoc2-depleted cells is a result of attenuated expression and secretion of LGALS3BP. Together our results suggest that Shoc2 regulates cell motility by modulating ERK1/2 signals to cell adhesion.

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Shoc2-tranduced ERK1/2 motility signals - Novel insights from functional genomics

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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