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.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, United States.
authors.forename: Myoungkun
authors.initials: M
authors.lastname: Jeoung
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, United States.
authors.forename: Eun Ryoung
authors.initials: ER
authors.lastname: Jang
authors.affiliation: Markey Cancer Center and Department of Biostatistics, University of Kentucky, Lexington, KY 40536, United States.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Markey Cancer Center and Department of Biostatistics, University of Kentucky, Lexington, KY 40536, United States.
authors.forename: Chi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40292, United States.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Rouchka
authors.affiliation: Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY 40292, United States; Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40292, United States.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, United States. Electronic address: emilia.galperin@uky.edu.
authors.forename: Emilia
authors.initials: E
authors.lastname: Galperin
mesh_terms: D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000235:genetics; D002522:Chlorocebus aethiops; D023281:Genomics; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Adhesion; ERK1/2; LGALS3BP; Motility; Shoc2 scaffold; Transcription