title: Temporal decoding of MAP kinase and CREB phosphorylation by selective immediate early gene expression.
abstract: A wide range of growth factors encode information into specific temporal patterns of MAP kinase (MAPK) and CREB phosphorylation, which are further decoded by expression of immediate early gene products (IEGs) to exert biological functions. However, the IEG decoding system remain unknown. We built a data-driven based on time courses of MAPK and CREB phosphorylation and IEG expression in response to various growth factors to identify how signal is processed. We found that IEG expression uses common decoding systems regardless of growth factors and expression of each IEG differs in upstream dependency, switch-like response, and linear temporal filters. Pulsatile ERK phosphorylation was selectively decoded by expression of EGR1 rather than c-FOS. Conjunctive NGF and PACAP stimulation was selectively decoded by synergistic JUNB expression through switch-like response to c-FOS. Thus, specific temporal patterns and combinations of MAPKs and CREB phosphorylation can be decoded by selective IEG expression via distinct temporal filters and switch-like responses. The data-driven modeling is versatile for analysis of signal processing and does not require detailed prior knowledge of pathways.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takeshi H
authors.initials: TH
authors.lastname: Saito
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Uda
authors.forename: Takaho
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D000841:Anisomycin; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases