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.

Protective Effects of Blueberry Anthocyanins against H2O2-Induced Oxidative Injuries in Human Retinal Pigment Epithelial Cells

“…46 The ERK-signaling pathway is involved in cell proliferation, survival, and differentiation. 47 The extracellularsignal-regulated kinases 1 and 2 (ERK1 and ERK2) are highly homologous and function in the same protein-kinase cascade, so they are often referred to collectively as ERK1/2. p38 kinases participate in a signaling cascade that controls cellular responses to inflammation as well as apoptosis.…”

“…Four distinct MAPK cascades (ERK, JNK, p38, and BMK/ERK5) have been elucidated that are activated by phosphorylation . The ERK-signaling pathway is involved in cell proliferation, survival, and differentiation . The extracellular-signal-regulated kinases 1 and 2 (ERK1 and ERK2) are highly homologous and function in the same protein-kinase cascade, so they are often referred to collectively as ERK1/2.…”

Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP–Dynein Complex

“…For this purpose, we subjected the cells to mild permeabilization with digitonin, conditions that were shown by others (27) and by us (28,29) to allow leakage of the cytosol and enable better visibility of intracellular compartments. Indeed, under these conditions, the fluorescence signal of ectopically expressed GFP was completely lost (Supplemental Fig.…”

Navigating the ERK1/2 MAPK Cascade

“…Although loss of either ERK gene impairs neuronal development [104], ERK1−/− mice are viable and fertile [105], while whole body ERK2 knockout results in embryonic lethality regardless of ERK1 expression [106]. Other work has reported divergent roles in specific contexts [107][108][109][110][111][112]. Phenotypic differences have been attributed to the allele number and differential expression of each isoform.…”