Trans-signaling by cytokine and growth factor receptors

Castellino, Alexander M.; Chao, Moses V.

doi:10.1016/s1359-6101(96)00038-x

Cited by 21 publications

(15 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PD98059 is a specific inhibitor for MKK1 and -2 (56), upstream kinases that phosphorylate and activate ERK (15,57). Although all drugs have the potential to exhibit nonspecific effects, we used PD98059 at concentrations (20 and 40 M) that are known to have no effect on other related MAP kinases including Jun N-terminal kinase and p38 (56).…”

Section: The Pi 3-kinase Signaling Pathway Is Activated By Bdnf In Comentioning

confidence: 99%

“…Many growth factors and neurotrophins can promote neuronal survival, including insulin, insulin-like growth factor-1, BDNF, nerve-growth factor (NGF), and neurotrophins 3 and 4/5 (11)(12)(13)(14). These factors can also activate several intracellular signaling transduction systems including the ERK and the PI 3-kinase pathways (15,16). Activation of the PI 3-kinase pathway is required for NGF-mediated survival of PC12 cells and SCG neurons (17,18), for insulin-like growth factor-1-mediated survival of cerebellar granule neurons, oligodendrocytes, and PC12 cells (19 -22), and for membrane depolarization-mediated survival of cerebellar granule neurons (20).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Neuroprotection by Brain-derived Neurotrophic Factor Is Mediated by Extracellular Signal-regulated Kinase and Phosphatidylinositol 3-Kinase

Hetman

Kanning²,

Cavanaugh

et al. 1999

Journal of Biological Chemistry

518

500

View full text Add to dashboard Cite

Apoptosis is a form of programmed cell death that plays a pivotal role during development and in the homeostasis of the adult nervous systems. However, mechanisms that regulate neuronal apoptosis are not well defined. Here, we report that brain-derived neurotrophic factor (BDNF) protects cortical neurons against apoptosis induced by camptothecin or serum deprivation and activates the extracellular-signal-regulated kinase (ERK) and the phosphatidylinositol 3-kinase (PI 3-kinase) pathways. Using pharmacological agents and transient transfection with dominant interfering or constitutive active components of the ERK or the PI 3-kinase pathway, we demonstrate that the ERK pathway plays a major role in BDNF neuroprotection against camptothecin. Furthermore, ERK is activated in cortical neurons during camptothecin-induced apoptosis, and inhibition of ERK increases apoptosis. In contrast, the PI 3-kinase pathway is the dominant survival mechanism for serum-dependent survival under normal culture conditions and for BDNF protection against serum withdrawal. These results suggest that the ERK pathway is one of several neuroprotective mechanisms that are activated by stress to counteract death signals in central nervous system neurons. Furthermore, the relative contribution of the ERK and PI 3-kinase pathways to neuronal survival may depend on the type of cellular injury.

show abstract

Section: The Pi 3-kinase Signaling Pathway Is Activated By Bdnf In Comentioning

confidence: 99%

mentioning

confidence: 99%

Neuroprotection by Brain-derived Neurotrophic Factor Is Mediated by Extracellular Signal-regulated Kinase and Phosphatidylinositol 3-Kinase

Hetman

Kanning²,

Cavanaugh

et al. 1999

Journal of Biological Chemistry

518

500

View full text Add to dashboard Cite

show abstract

“…Interestingly enough, IL-6 may bind to sIL-6Ra forming an IL-6/sIL-6Ra complex which is able to bind membrane gp130, leading to signal transduction. Activation mediated by ligand/soluble receptor subunits is called trans-signalling (14). In contrast, sgp130 may bind soluble and membrane-bound IL-6/IL-6Ra complexes and prevent interaction with membrane gp130, hence signal transduction.…”

Section: Introductionmentioning

confidence: 99%

High-dose glucocorticoids increase serum levels of soluble IL-6 receptor α and its ratio to soluble gp130: an additional mechanism for early increased bone resorption

Dovio¹,

Perazzolo²,

Saba³

et al. 2006

eur j endocrinol

View full text Add to dashboard Cite

Objective: Glucocorticoids (GCs) at pharmacological doses stimulate bone resorption. Mechanisms of this action are unclear. The osteoclastogenic cytokine interleukin (IL)-6 acts through an oligomeric receptor consisting of two subunits, gp80 (or IL-6 receptor a, IL-6Ra) and gp130; both exist in membrane and soluble forms. Soluble IL-6Ra (sIL-6Ra) enhances, while sgp130 inhibits IL-6 signalling. In vitro, GCs enhance many effects of IL-6 by up-regulation of IL-6Ra. The aim of the present study was to assess acute changes of IL-6 system in the peripheral blood of patients given high-dose GCs. Subjects and methods: Serum levels of IL-6, sIL-6Ra, sgp130 and bone turnover markers were assessed before and each day during treatment in 24 multiple sclerosis (MS) patients undergoing high-dose (prednisolone, 15 mg/kg per day), short-term (3 to 5 days) intravenous GC therapy for relapse at the Regional Multiple Sclerosis Centre. Results: An immediate and marked fall of osteocalcin and an early increase of C-terminal telopeptide of type I collagen were already noticed at day 2 (P , 0.001 and P , 0.02, respectively); both became more apparent in the subsequent days. IL-6 was always below or near the detection limit of our ELISA. sgp130 showed a slight increase. sIL-6Ra significantly increased, peaking at day 4 (P , 0.01). However, inter-individual variability of response was noticed. Four patients showed a slight decrease, while no change was observed in one patient and an increase was noticed in the remaining nineteen (maximum change ranging from þ10% to þ67% with respect to baseline). In these patients, a significant increase of sIL-6Ra/sgp130 ratio was apparent. No correlation was found between bone turnover markers and any measured component of the IL-6 system. Conclusions: sIL-6Ra and sIL-6Ra/sgp130 ratio are precociously increased in the peripheral blood of the vast majority of patients given high-dose, intravenous GCs. The increase of systemically available sIL-6Ra conceivably results in the enhancement of IL-6-dependent osteoclastogenesis. The role of such a mechanism in the bone loss observed in inflammatory and immune-mediated diseases (where abundancy of IL-6 in the bone microenvironment is expected) requires further investigation. European Journal of Endocrinology 154 745-751

show abstract

“…Ligands for G protein-coupled receptors are capable of activating the mitogen-activated protein (MAP) kinase signaling pathway, in addition to classic G protein-dependent signaling pathways involving adenylyl cyclase and phospholipase C (12,13). Induction of mitogenic receptor tyrosine kinase phosphorylation also occurs through signaling from several G proteincoupled receptors (14).…”

mentioning

confidence: 99%

Activation of Trk neurotrophin receptors in the absence of neurotrophins

Lee

Chao

2001

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

441

334

View full text Add to dashboard Cite

Neurotrophins regulate neuronal cell survival and synaptic plasticity through activation of Trk receptor tyrosine kinases. Binding of neurotrophins to Trk receptors results in receptor autophosphorylation and downstream phosphorylation cascades. Here, we describe an approach to use small molecule agonists to transactivate Trk neurotrophin receptors. Activation of TrkA receptors in PC12 cells and TrkB in hippocampal neurons was observed after treatment with adenosine, a neuromodulator that acts through G protein-coupled receptors. These effects were reproduced by using the adenosine agonist CGS 21680 and were counteracted with the antagonist ZM 241385, indicating that this transactivation event by adenosine involves adenosine 2A receptors. The increase in Trk activity could be inhibited by the use of the Src family-specific inhibitor, PP1, or K252a, an inhibitor of Trk receptors. In contrast to other G protein-coupled receptor transactivation events, adenosine used Trk receptor signaling with a longer time course. Moreover, adenosine activated phosphatidylinositol 3-kinase͞Akt through a Trk-dependent mechanism that resulted in increased cell survival after nerve growth factor or brain-derived neurotrophic factor withdrawal. Therefore, adenosine acting through the A 2A receptors exerts a trophic effect through the engagement of Trk receptors. These results provide an explanation for neuroprotective actions of adenosine through a unique signaling mechanism and raise the possibility that small molecules may be used to elicit neurotrophic effects for the treatment of neurodegenerative diseases.

show abstract

Trans-signaling by cytokine and growth factor receptors

Cited by 21 publications

References 53 publications

Neuroprotection by Brain-derived Neurotrophic Factor Is Mediated by Extracellular Signal-regulated Kinase and Phosphatidylinositol 3-Kinase

Neuroprotection by Brain-derived Neurotrophic Factor Is Mediated by Extracellular Signal-regulated Kinase and Phosphatidylinositol 3-Kinase

High-dose glucocorticoids increase serum levels of soluble IL-6 receptor α and its ratio to soluble gp130: an additional mechanism for early increased bone resorption

Activation of Trk neurotrophin receptors in the absence of neurotrophins

Contact Info

Product

Resources

About