The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor

Soppet, Daniel; Escandón, Enrique; Maragos, Johnne; Middlemas, David S.; Raid, Susan W.; Blair, Janet; Burton, Louis E.; Stanton, Brian R.; Kaplan, David R.; Hunter, Tony; Nikolics, Károly; Parade, Luis F.

doi:10.1016/0092-8674(91)90396-g

Cited by 761 publications

(399 citation statements)

References 48 publications

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“…However, the efficacy of the interference of the L2A or L2B peptides with the binding of the various neurotrophins was not as great as could be expected from previous experiments involving recombinant proteins [39]. Calculation of the inhibition constants for the interaction between the peptides and the neurotrophins yielded K~ values in the range of 2 × 10 -8 M to 1 × 10 -7 M which is at least a factor 20 short of the affinities observed on recombinant receptors as well as on cells ectopically expressing TrkA [9,22] or TrkB [3,31] receptors. This supports our interpretation of the low capacity observed with L2A and L2B affinity columns, i.e.…”

Section: Resultsmentioning

confidence: 55%

“…TrkA is the biologically functional receptor for nerve growth factor (NGF) [9,13], whereas its homolog TrkB binds three different neurotrophins [3,8,16,24,36] namely brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) [5,14,15,31,32]. The extracellular domains of Trk-type receptors harbor a modular mosaic of potential ligand binding modules, namely two immunoglobulin (Ig)-like domains and an LRM3-cassette consisting of a tandem array of three leucine-rich motifs (LRMs) flanked by cysteine-rich clusters [28].…”

Section: Introductionmentioning

confidence: 99%

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Specific neurotrophin binding to leucine‐rich motif peptides of TrkA and TrkB

et al. 1995

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Section: Resultsmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Specific neurotrophin binding to leucine‐rich motif peptides of TrkA and TrkB

et al. 1995

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“…In contrast, neurotrophin 3 (NT-3) has been reported to inhibit FGF-2-induced Akt activation as well as Akt-induced neuronal proliferation (Jin et al, 2005). We similarly found that the activation of ERK stimulated by co-treatment with FGF-2 and BDNF, which shares similarities to NT-3 (Soppet et al, 1991), was less than additive. It is possible that receptors for these 2 peptides activate pathways that exhibit negative interactions.…”

Section: Discussionmentioning

confidence: 78%

Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures

Johnson-Farley¹,

Patel²,

Kim³

et al. 2007

Brain Research

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The significance of multiple growth factors acting on individual neurons in the central nervous system is presently unclear. Cultured hippocampal neurons were used in the present study to compare the neurotrophic actions of fibroblast growth factor-2 (FGF-2) with the better characterized growth factors, insulin-like growth factor (IGF)-1 and brain-derived neurotrophic factor (BDNF). Additionally, cultures were utilized to identify possible interactions between FGF-2 and the other growth factors. Activation of the ERK and Akt pro-survival pathways, as well as neuronal survival itself, were studied. The maximal magnitude of Akt activation stimulated by FGF-2 was found to be similar to that stimulated by IGF-1 and BDNF. In contrast, IGF-1 was less effective at inducing ERK activation than were BDNF and FGF-2. All three agents were found to promote survival of neurons cultured under serum-free, low-insulin conditions, with FGF-2 surprisingly being significantly more effective than the other two peptides. Co-treatment with maximal concentrations of either IGF-1 or BDNF enhanced FGF-2-stimulated Akt and ERK activation. However, no enhancement of survival beyond that stimulated by FGF-2 was observed with co-treatment. These findings suggest that FGF-2 may play an important role in promoting the survival of hippocampal neurons. Additionally, an interesting dissociation was identified between the positive interaction of FGF-2 with both IGF-1 and BDNF in activating Akt and ERK, and the lack of enhancement of FGF-2-induced neuroprotection.

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“…Our control using CD4 + Molt4 cells did not reveal induction of tyrosine phosphorylation in response to rgp 120, which is in accordance with the results of Horak et al (1990) forT lymphocytes. Tyrosine phosphorylation of proteins with molecular masses in the range of 110 to 140 kDa has been described to occur after activation of many cell surface receptors on brain cells including receptors for neurotrophic factors (Soppet et al, 1991;Squinto et al, 1991 ), the interleukin-6 receptor (Hibi et al, 1990), and receptors of the integrin family (Kornberg et a/., 1991 ). lt will be of great interest to identify the nature of the receptor complex we found and the tyrosine kinase involved.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase

Schneider-Schaulies¹,

Schneider‐Schaulies²,

Brinkmann³

et al. 1992

Virology

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Human immunodeficiency virus (HIV-1) infection in the human brain Ieads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp 120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on int~acellular.s.ignallin~. Herewe pre~ent evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatlde, spec1f1cally bmds to a protem receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) pre~ent. on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rap1dly 1nduced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130-and 115-kDa p~oteins. The c~ncentration of intracellular calciumwas not affected by rgp120 in these cells. Our data suggest a novel Signal transduc1ng HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.

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The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor

Cited by 761 publications

References 48 publications

Specific neurotrophin binding to leucine‐rich motif peptides of TrkA and TrkB

Specific neurotrophin binding to leucine‐rich motif peptides of TrkA and TrkB

Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures

HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase

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