title: Dynamics and variability of ERK2 response to EGF in individual living cells.
abstract: Signal-transduction cascades are usually studied on cell averages, masking variability between individual cells. To address this, we studied in individual cells the dynamic response of ERK2, a well-characterized MAPK signaling protein, which enters the nucleus upon stimulation. Using fluorescent tagging at the endogenous chromosomal locus, we found that cells show wide basal variation in ERK2 nuclear levels. Upon EGF stimulation, cells show (1) a fold-change response, where peak nuclear accumulation of ERK2 is proportional to basal level in each cell; and (2) exact adaptation in nuclear levels of ERK2, returning to original basal level of each cell. The timing of ERK2 dynamics is more precise between cells than its amplitude. We further found that in some cells ERK2 exhibits a second pulse of nuclear entry, smaller than the first. The present study suggests that this signaling system compensates for natural biological noise: despite large variation in nuclear basal levels, ERK2's fold dynamics is similar between cells.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100 Israel.
authors.forename: Cellina
authors.initials: C
authors.lastname: Cohen-Saidon
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Cohen
authors.forename: Alex
authors.initials: A
authors.lastname: Sigal
authors.forename: Yuvalal
authors.initials: Y
authors.lastname: Liron
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D008164:Luminescent Proteins; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1