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Signaling Diversity Enabled by Rap1 and cAMP/PKA‐Regulated Plasma Membrane ERK with Distinct Temporal Dynamics
Author(s) -
Keyes Jeremiah,
Ganesan Ambhighainath,
Molinar-Inglis Olivia,
Hamidzadeh Archer,
Ling Megan,
Trejo JoAnn,
Levchenko Andre,
Zhang Jin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00680
Subject(s) - mapk/erk pathway , microbiology and biotechnology , extracellular , activator (genetics) , signal transduction , rap1 , chemistry , subcellular localization , biology , biochemistry , gene , cytoplasm
A variety of different signals induce specific responses through a common, ERK‐dependent kinase cascade. It has been suggested that signaling specificity can be achieved through precise temporal regulation of ERK activity. Given the wide distrubution of ERK susbtrates across different subcellular compartments, it is important to understand how ERK activity is temporally regulated at specific subcellular locations. To address this question, we expanded the toolbox of FRET‐based ERK biosensors by creating a series of improved biosensors targeted to various subcellular regions via sequence specific motifs to measure spatiotemporal changes in ERK enzymatic activity. Using these sensors, we showed that EGF induces sustained ERK activity near the plasma membrane in sharp contrast to the transient activity observed in the cytopolasm and nucleus. Furthermore, EGF‐induced plasma membrane ERK activity is regulated by Rap1, a noncanonical activator, and the cAMP/PKA signaling axis. We report that plasma membrane ERK controls cell morphology and EGF‐induced membrane protrusion dynamics. Our work strongly supports that spatial and temporal regulation of ERK activity is integrated to control signaling specificity from a single extracellular signal to multiple cellular processes. Support or Funding Information This work is supported by NIH R35 CA197622, R01 DK073368 (to J.Z). J.K. and O.M.I are supported by a post‐doctoral fellowship from NIH/NIGMS (K12GM068524). The development of Rap1 sensors at CISMM was supported by 5P41‐EB002025.