Sustained Signaling by Phospholipase C-γ Mediates Nerve Growth Factor-Triggered Gene Expression

Choi, Deog-Young; Toledo‐Aral, Juan José; Segal, Rosalind A.; Halegoua, Simon

doi:10.1128/mcb.21.8.2695-2705.2001

Cited by 45 publications

(33 citation statements)

References 50 publications

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“…Similar results were observed previously (34). It was shown that these transient events trigger stimulation of intercellular molecules and induce longterm activation of intracellular signals (35,36). From these results, the transient decrease of cofilin phosphorylation may trigger intracellular machinery that increases the proliferation of RASMCs.…”

Section: Discussionsupporting

confidence: 77%

Cofilin Phosphorylation Mediates Proliferation in Response to Platelet-Derived Growth Factor-BB in Rat Aortic Smooth Muscle Cells

Won

Park

et al. 2008

J Pharmacol Sci

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Abstract. Cofilin, an actin-binding protein, is essential for a variety of cell responses. In this study, we investigated the correlation between proliferation and cofilin phosphorylation in response to platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells (RASMCs). The phosphorylation of cofilin and activity of mitogen-activated protein kinase (MAPK) were measured by Western analyses and proliferation in RASMCs was measured by BrdU incorporation assays. The phosphorylation of cofilin in RASMCs was decreased by PDGF-BB treatment at 10 min, but recovered to the level of the quiescent state at 60 min. PDGF-BB-induced dephosphorylation of cofilin was inhibited by pretreatment with piceatannol (a spleen tyrosine kinase [Syk] inhibitor), PP2 (a Src inhibitor), or SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), but not by PD98059, an inhibitor of extracellular signal-regulated kinase 1 / 2. PDGF-BB increased JNK activity and proliferation, and these responses were suppressed by kinase inhibitors and small interference RNA-cofilin. The results suggest that PDGF-BB-induced dephosphorylation of cofilin can be promoted via the JNK pathway, which is regulated by both Syk and Src kinases and that cofilin dephosphorylation may be involved in PDGF-BB-induced RASMC proliferation.

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Section: Discussionsupporting

confidence: 77%

Cofilin Phosphorylation Mediates Proliferation in Response to Platelet-Derived Growth Factor-BB in Rat Aortic Smooth Muscle Cells

Won

Park

et al. 2008

J Pharmacol Sci

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“…In PC12 cells, a 1-2 min treatment of NGF rapidly phosphorylates PLC-␥ through the activation of the TrkA receptor tyrosine kinase, in which the autophosphorylation of the TrkA receptor and the phosphorylation of PLC-␥ are sustained for up to 30 min and 2 h, respectively (58). We observed that the activation of PLC was not important for the maintenance of BDNF-induced sustained intracellular Ca 2ϩ elevation (Fig.…”

Section: Discussionmentioning

confidence: 53%

Brain-Derived Neurotrophic Factor Induces Sustained Elevation of Intracellular Ca2+ in Rodent Microglia

Mizoguchi

Monji

Kato

et al. 2009

The Journal of Immunology

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Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, NO, and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we observed that BDNF induced a sustained increase in [Ca2+]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosin-related kinase B-T1 receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, pretreatment of BDNF suppressed the IFN-γ-induced increase in [Ca2+]i, along with a rise in basal levels of [Ca2+]i in rodent microglial cells. We show direct evidence that rodent microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

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“…In other RTKs, recruitment of different adaptor proteins to distinct phosphotyrosine docking sites leads to activation of disparate signaling pathways, which are often coupled to different biological responses (Madhani, 2001;Pawson and Scott, 1997). For example, in TrkA, the receptor for nerve growth factor, phosphorylation of a juxtamembrane tyrosine leads to Ras and PI3-kinase activation, which are important for cell survival and neurite outgrowth (Greene and Kaplan, 1995;Huang and Reichardt, 2001), whereas phosphorylation of a tyrosine in the C-terminal region of TrkA leads to PLCγ activation, which is crucial for NGF-dependent Na + channel and VRI channel regulation (Choi et al, 2001;Chuang et al, 2001). Moreover, in TrkB, phosphorylation of a single juxtamembrane tyrosine is required for nearly all of NT4-dependent signaling whereas phosphorylation of other tyrosine residues are required to mediate BDNF-dependent signaling in vivo (Minichiello et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Restoration of synapse formation inMuskmutant mice expressing a Musk/Trk chimeric receptor

Herbst

Avetisova²,

Burden³

2002

Development

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Development 129, [5449][5450][5451][5452][5453][5454][5455][5456][5457][5458][5459][5460] On page 5454 of this article, the first paragraph in the section 'Motor axons extend…' should read 'Based on the expression of transgenes containing the MCK enhancer and promoter, the endogenous MCK gene is activated in skeletal muscle at ~E13.5 (S. Hauschka, personal communication), 1 day after motor axons first enter the muscle.'We apologise to the authors and readers for this mistake. ERRATUM INTRODUCTIONNeuromuscular synapses form following a series of complex interactions between motor neurons, muscle fibers and Schwann cells (Burden, 1998;Sanes and Lichtman, 1999;Schaeffer et al., 2001;Son and Thompson, 1995). Agrin, a 200 kDa protein synthesized by motor neurons, is a critical synaptic signaling molecule that organizes postsynaptic differentiation by stimulating Musk, a receptor tyrosine kinase (RTK) expressed selectively in skeletal muscle McMahan, 1990). Embryos lacking agrin or Musk fail to form neuromuscular synapses and consequently die at birth due to their failure to move or breathe (DeChiara et al., 1996;Gautam et al., 1996). Neurogenesis and myogenesis appear normal in agrin and Musk mutant embryos, but skeletal muscle-derived proteins, including acetylcholine receptors (AChRs), which are normally concentrated at synaptic sites, are instead expressed uniformly in muscle of Musk mutant mice. In addition, AChR genes, which are transcribed selectively in synaptic nuclei of wild-type mice, are expressed throughout the myofiber of Musk mutant mice. Presynaptic differentiation is also aberrant in agrin and Musk mutant mice, as motor axons fail to stop or differentiate and instead wander throughout the muscle. Taken together with experiments showing that Musk is activated by agrin, these results indicate that agrin stimulation of Musk leads to clustering of critical musclederived proteins, including AChRs, activation of synapsespecific gene expression and the induction and/or reorganization of a retrograde signal for presynaptic differentiation (DeChiara et al., 1996;Gautam et al., 1996;Glass et al., 1996). Domains in Musk that are important for Musk signaling have been defined by introducing wild-type or mutant forms of Musk into Musk mutant muscle cell lines (Herbst and Burden, 2000;Zhou et al., 1999). These studies have revealed an essential role for one of the two juxtamembrane tyrosine residues in Musk (Y553), as mutation of this tyrosine abrogates the ability of agrin to induce clustering or tyrosine phosphorylation of AChRs in cultured myotubes. This tyrosine appears to have a dual function in Musk signaling, as this tyrosine is required both to activate Musk kinase activity fully and to recruit a signaling component(s) that functions downstream from Musk (Herbst and Burden, 2000). Evidence for such a dual role is based upon analysis of Musk/TrkA chimeric receptors. Agrin stimulates tyrosine phosphorylation of a chimeric receptor composed of the extracellular and transmembrane regions of Musk, and the intrac...

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Sustained Signaling by Phospholipase C-γ Mediates Nerve Growth Factor-Triggered Gene Expression

Cited by 45 publications

References 50 publications

Cofilin Phosphorylation Mediates Proliferation in Response to Platelet-Derived Growth Factor-BB in Rat Aortic Smooth Muscle Cells

Cofilin Phosphorylation Mediates Proliferation in Response to Platelet-Derived Growth Factor-BB in Rat Aortic Smooth Muscle Cells

Brain-Derived Neurotrophic Factor Induces Sustained Elevation of Intracellular Ca2+ in Rodent Microglia

Restoration of synapse formation inMuskmutant mice expressing a Musk/Trk chimeric receptor

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