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

14 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

Publisher Copyright:
© 2016 Elsevier Inc.

Funding

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. 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

Funders	Funder number
Markey Cancer Center
Markey Cancer Center NCI
University of Kentucky Markey Cancer Center
Cores Science and Engineering Ltd.
National Institutes of Health (NIH)	R01GM113087
National Institutes of Health (NIH)
American Cancer Society-Michigan Cancer Research Fund	RSG-14-172-01-CSM
American Cancer Society-Michigan Cancer Research Fund
National Childhood Cancer Registry – National Cancer Institute	K99CA126161, P30CA177558
National Childhood Cancer Registry – National Cancer Institute
National Institute of General Medical Sciences	P20GM103486, P20GM103436
National Institute of General Medical Sciences
National Center for Research Resources
Center for Outcomes Research and Evaluation, Yale School of Medicine
Office of the Vice President for Research, University of South Carolina

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

Cite this

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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.",

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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