Regulation of α2B-Adrenergic Receptor-mediated Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Activation by ADP-ribosylation Factor 1

Dong, Chunmin; Li, Chunman; Wu, Guangyu

doi:10.1074/jbc.m111.267286

Cited by 26 publications

(47 citation statements)

References 51 publications

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“…During the studies of regulation of GPCR trafficking and signaling by ARFs [27, 28], we found that the activation the MAPK Raf1-MEKERK1/2 pathway by α 2B -adrenergic receptor (α 2B -AR), a typical GPCR, may be partially mediated through ARF1 [29]. In the current study, we have further defined the underlying molecular mechanism and the possible function of this ARF1-mediated MAPK signaling pathway.…”

Section: Introductionmentioning

confidence: 75%

“…[ 3 H]-RX821002 (specific activity = 50 Ci/mmol) was from Perkin Elmer Life Sciences. All other materials were obtained as described elsewhere [29-31]. …”

Section: Methodsmentioning

confidence: 99%

“…The cells were solubilized by addition of 300 μl SDS gel loading buffer and 20 μl of total cell lysate was separated by SDS-PAGE. Activation of ERK1/2 and RSK1 was determined by immunoblotting measuring their phosphorylation with phosphor-specific antibodies as described previously [29, 30]. …”

Section: Methodsmentioning

confidence: 99%

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The mechanism and function of mitogen-activated protein kinase activation by ARF1

Zhou

Dong

Davis

et al. 2015

Cellular Signalling

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Mitogen-activated protein kinases (MAPK) can be activated by a number of biochemical pathways through distinct signaling molecules. We have recently revealed a novel function for the Ras-like small GTPase ADP-ribosylation factor 1 (ARF1) in mediating the activation of Raf1-MEK-ERK1/2 pathway by G protein-coupled receptors. Here, we have further defined the underlying mechanism and the possible function of ARF1-mediated MAPK pathway. We demonstrated that the blockage of ARF1 activation and the disruption of ARF1 localization to the Golgi by mutating Thr48, a highly conserved residue involved in the exchange of GDP for GTP, and the myristoylation site Gly2 abolished ARF1's ability to activate ERK1/2. In addition, treatment with Golgi structure disrupting agents markedly attenuated ARF1-mediated ERK1/2 activation. Furthermore, ARF1 significantly promoted cell proliferation. More interestingly, ARF1 activated 90kDa ribosomal S6 kinase 1 (RSK1) without influencing Elk-1 activation and ERK2 translocation to the nuclei. These data demonstrate that, once activated, ARF1 activates the MAPK pathway likely using the Golgi as a main platform, which in turn activates the cytoplasmic RSK1, leading to cell proliferation.

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Section: Introductionmentioning

confidence: 75%

“…[ 3 H]-RX821002 (specific activity = 50 Ci/mmol) was from Perkin Elmer Life Sciences. All other materials were obtained as described elsewhere [29-31]. …”

Section: Methodsmentioning

confidence: 99%

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The mechanism and function of mitogen-activated protein kinase activation by ARF1

Zhou

Dong

Davis

et al. 2015

Cellular Signalling

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“…All three ␣ 2 -ARs couple to the Gi/Go family G proteins, and their activation has been well shown to stimulate the mitogen-activated protein kinases (MAPK) ERK1/2, inhibit adenylyl cyclases, and suppress voltage-gated calcium channels (24,26,(37)(38)(39). To investigate if GGA3 knockdown-induced reduction of cell surface ␣ 2B -AR expression could result in a concomitant defective signaling, the activation of ERK1/2 and the reduction of cAMP production were chosen as functional readouts.…”

Section: Resultsmentioning

confidence: 99%

“…Cyclic AMP (cAMP) concentrations were measured by using the Cyclic AMP XP Assay kit (Cell Signaling Technology) as described previously (26). Briefly, HEK293 cells inducibly expressing ␣ 2B -AR were cultured in 6-well dishes and transfected with GGA3 siRNA or shRNA for 36 h and then incubated with tetracycline at 40 ng/ml for 24 h. The cells were then split into 96-well plates at a density of 1 ϫ 10 4 cells/well.…”

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confidence: 99%

GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export

Zhang

Davis

et al. 2016

Molecular and Cellular Biology

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Molecular mechanisms governing the anterograde trafficking of nascent G protein-coupled receptors (GPCRs) are poorly understood. Here, we have studied the regulation of cell surface transport of ␣ 2 -adrenergic receptors (␣ 2 -ARs) by GGA3 (Golgi-localized, ␥-adaptin ear domain homology, ADP ribosylation factor-binding protein 3), a multidomain clathrin adaptor protein that sorts cargo proteins at the trans-Golgi network (TGN) to the endosome/lysosome pathway. By using an inducible system, we demonstrated that GGA3 knockdown significantly inhibited the cell surface expression of newly synthesized ␣ 2B -AR without altering overall receptor synthesis and internalization. The receptors were arrested in the TGN. Furthermore, GGA3 knockdown attenuated ␣ 2B -AR-mediated signaling, including extracellular signal-regulated kinase 1/2 (ERK1/2) activation and cyclic AMP (cAMP) inhibition. More interestingly, GGA3 physically interacted with ␣ 2B -AR, and the interaction sites were identified as the triple Arg motif in the third intracellular loop of the receptor and the acidic motif EDWE in the VHS domain of GGA3. In contrast, ␣ 2A -AR did not interact with GGA3 and its cell surface export and signaling were not affected by GGA3 knockdown. These data reveal a novel function of GGA3 in export trafficking of a GPCR that is mediated via a specific interaction with the receptor.

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Alpha-Adrenoceptor Modulation in Central Nervous System Trauma: Pain, Spasms, and Paralysis - An Unlucky Triad

et al. 2014

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Many researchers have attempted to pharmacologically modulate the adrenergic system to control locomotion, pain, and spasms after central nervous system (CNS) trauma, although such efforts have led to conflicting results. Despite this, multiple studies highlight that α-adrenoceptors (α-ARs) are promising therapeutic targets because in the CNS, they are involved in reactivity to stressors and regulation of locomotion, pain, and spasms. These functions can be activated by direct modulation of these receptors on neuronal networks in the brain and the spinal cord. In addition, these multifunctional receptors are also broadly expressed on immune cells. This suggests that they might play a key role in modulating immunological responses, which may be crucial in treating spinal cord injury and traumatic brain injury as both diseases are characterized by a strong inflammatory component. Reducing the proinflammatory response will create a more permissive environment for axon regeneration and may support neuromodulation in combination therapies. However, pharmacological interventions are hindered by adrenergic system complexity and the even more complicated anatomical and physiological changes in the CNS after trauma. This review is the first concise overview of the pros and cons of α-AR modulation in the context of CNS trauma.

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Regulation of α2B-Adrenergic Receptor-mediated Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Activation by ADP-ribosylation Factor 1

Cited by 26 publications

References 51 publications

The mechanism and function of mitogen-activated protein kinase activation by ARF1

The mechanism and function of mitogen-activated protein kinase activation by ARF1

GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export

Alpha-Adrenoceptor Modulation in Central Nervous System Trauma: Pain, Spasms, and Paralysis - An Unlucky Triad

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