scholarly journals Signaling Diversity Enabled by Rap1-Regulated Plasma Membrane ERK with Distinct Temporal Dynamics

2019 ◽  
Author(s):  
Jeremiah Keyes ◽  
Ambhighainath Ganesan ◽  
Olivia Molinar-Inglis ◽  
Archer Hamidzadeh ◽  
Megan Ling ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Temporal Dynamics ◽  
Membrane Protrusion ◽  
Signaling Specificity ◽  
Temporal Regulation ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Transient Activity ◽  
Kinase Cascade ◽  
Erk Activity

AbstractA 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 distrubtion 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 have 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 involves Rap1, a noncanonical activator, and 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.

scholarly journals Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeremiah Keyes ◽  
Ambhighainath Ganesan ◽  
Olivia Molinar-Inglis ◽  
Archer Hamidzadeh ◽  
Jinfan Zhang ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Temporal Dynamics ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Signaling Specificity ◽  
Temporal Regulation ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Transient Activity ◽  
Erk Activity

A variety of different signals induce specific responses through a common, extracellular-signal regulated kinase (ERK)-dependent cascade. It has been suggested that signaling specificity can be achieved through precise temporal regulation of ERK activity. Given the wide distrubtion 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 have expanded the toolbox of Förster Resonance Energy Transfer (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 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 cytoplasm and nucleus. Furthermore, EGF-induced plasma membrane ERK activity involves Rap1, a noncanonical activator, and 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.

scholarly journals Extracellular Signal-Regulated Kinase 1c (ERK1c), a Novel 42-Kilodalton ERK, Demonstrates Unique Modes of Regulation, Localization, and Function

2004 ◽  
Vol 24 (22) ◽  
pp. 10000-10015 ◽  
Author(s):  
Daniel M. Aebersold ◽  
Yoav D. Shaul ◽  
Yuval Yung ◽  
Nirit Yarom ◽  
Zhong Yao ◽  
...  
Keyword(s):  
Cell Density ◽  
Differential Regulation ◽  
Dominant Negative ◽  
Signaling Specificity ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Extracellular Stimuli ◽  
Golgi Fragmentation ◽  
And Function ◽  
Rats And Mice

ABSTRACT Extracellular signal-regulated kinases (ERKs) are signaling molecules that regulate many cellular processes. We have previously identified an alternatively spliced 46-kDa form of ERK1 that is expressed in rats and mice and named ERK1b. Here we report that the same splicing event in humans and monkeys causes, due to sequence differences in the inserted introns, the production of an ERK isoform that migrates together with the 42-kDa ERK2. Because of the differences of this isoform from ERK1b, we named it ERK1c. We found that its expression levels are about 10% of ERK1. ERK1c seems to be expressed in a wide variety of tissues and cells. Its activation by MEKs and inactivation by phosphatases are slower than those of ERK1, which is probably the reason for its differential regulation in response to extracellular stimuli. Unlike ERK1, ERK1c undergoes monoubiquitination, which is increased with elevated cell density concomitantly with accumulation of ERK1c in the Golgi apparatus. Elevated cell density also causes enhanced Golgi fragmentation, which is facilitated by overexpression of native ERK1c and is prevented by dominant-negative ERK1c, indicating that ERK1c mediates cell density-induced Golgi fragmentation. The differential regulation of ERK1c extends the signaling specificity of MEKs after stimulation by various extracellular stimuli.

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

scholarly journals Modulation of Cell–Cell Interactions in Drosophila Oocyte Development

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 274
Author(s):  
Matthew Antel ◽  
Mayu Inaba
Keyword(s):  
Cell Communication ◽  
Cell Interaction ◽  
Oocyte Development ◽  
Suitable Model ◽  
Physiological Regulation ◽  
Temporal Regulation ◽  
Cellular Processes ◽  
Cellular Machinery ◽  
Drosophila Ovary ◽  
Cell Cell

The Drosophila ovary offers a suitable model system to study the mechanisms that orchestrate diverse cellular processes. Oogenesis starts from asymmetric stem cell division, proper differentiation and the production of fully patterned oocytes equipped with all the maternal information required for embryogenesis. Spatial and temporal regulation of cell-cell interaction is particularly important to fulfill accurate biological outcomes at each step of oocyte development. Progress has been made in understanding diverse cell physiological regulation of signaling. Here we review the roles of specialized cellular machinery in cell-cell communication in different stages of oogenesis.

scholarly journals Heat Shock Protein Hsp72 Controls Oncogene-Induced Senescence Pathways in Cancer Cells

2008 ◽  
Vol 29 (2) ◽  
pp. 559-569 ◽  
Author(s):  
Vladimir L. Gabai ◽  
Julia A. Yaglom ◽  
Todd Waldman ◽  
Michael Y. Sherman
Keyword(s):  
Heat Shock ◽  
Epithelial Cells ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Pi3k Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
P53 Pathway ◽  
Extracellular Signal ◽  
Kinase Cascade ◽  
Dependent Pathway

ABSTRACT The heat shock protein Hsp72 is expressed at the elevated levels in various human tumors, and its levels often correlate with poor prognosis. Previously we reported that knockdown of Hsp72 in certain cancer cells, but not in untransformed breast epithelial cells, triggers senescence via p53-dependent and p53-independent mechanisms. Here we demonstrate that the p53-dependent pathway controlled by Hsp72 depends on the oncogenic form of phosphatidylinositol 3-kinase (PI3K). Indeed, upon expression of the oncogenic PI3K, epithelial cells began responding to Hsp72 depletion by activating the p53 pathway. Moreover, in cancer cell lines, activation of the p53 pathway caused by depletion of Hsp72 was dependent on oncogenes that activate the PI3K pathway. On the other hand, the p53-independent senescence pathway controlled by Hsp72 was associated with the Ras oncogene. In this pathway, extracellular signal-regulated kinases (ERKs) were critical for senescence, and Hsp72 controlled the ERK-activating kinase cascade at the level of Raf-1. Importantly, upon Ras expression, untransformed cells started responding to knockdown of Hsp72 by constitutive activation of ERKs, culminating in senescence. Therefore, Hsp72 is intimately involved in suppression of at least two separate senescence signaling pathways that are regulated by distinct oncogenes in transformed cells, which explains why cancer cells become “addicted” to this heat shock protein.

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