title: The extra-cellular signal regulated kinases ERK1 and ERK2 segregate displaying distinct spatiotemporal characteristics in activated mast cells.
abstract: ERK1 and ERK2 are highly homologous isoforms that often play redundant roles in regulating cellular functions. We analyzed the spatiotemporal patterns of ERK1 and ERK2 in resting and activated mast cells. Strikingly, we identified distinct pathways for these kinases. ERK1 localized to the cytosol and translocated to the nucleus upon cell activation and kinase phosphorylation. In contrast, ERK2 distributed between the cytosol and near the microtubule organizing center (MTOC) in resting cells and accumulated further at a pericentrosomal region upon cell trigger. Pericentrosomal accumulation of ERK2 was phosphorylation independent, required an intact microtubule network and was significantly enhanced by the overexpression of Neuronal Calcium Sensor-1 (NCS-1). We also identified γ-tubulin and phosphatidylinositol 4 kinaseβ (PI4Kβ), a downstream effector of NCS-1, as novel partner proteins of ERK2. Taken together, our results imply non-redundant functions of ERK1 and ERK2 in mast cells and implicate NCS-1 and PΙ4Κβ as regulators of ERK2 trafficking.
authors: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Anat Benado
authors: AB
authors: Bar-Gill
authors: Adi
authors: A
authors: Efergan
authors: Rony
authors: R
authors: Seger
authors: Mitsunori
authors: M
authors: Fukuda
authors: Ronit
authors: R
authors: Sagi-Eisenberg
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D002522:Chlorocebus aethiops; D003600:Cytosol / Q000201:enzymology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology*; D022101:Microtubule-Organizing Center / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D014404:Tubulin; C101464:frequenin calcium sensor proteins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3