Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction.

Title

Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction.

Creator

Koo P H; Qiu W S

Publisher

The Journal of biological chemistry

Date

1994
1994-02

Description

Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit beta-nerve growth factor (NGF)-promoted neurite outgrowth and the survival of embryonic sensory and forebrain neurons, whereas normal alpha 2M has little or no such activity. The objective of this study is to elucidate the mechanism of inhibition by monoamine-activated alpha 2M. Methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) dose dependently inhibit NGF-promoted neurite outgrowth of the pheochromocytoma PC12 cell and its subline PC12(6-24) which overexpresses human trk protooncogene product, but have no effect on their viability, and this inhibition can be blocked by high concentrations of NGF. The binding of MA-alpha 2M to trk, which is a part of high-affinity NGF receptor, was studied with PC12(6-24) cells and NIH-3T3 fibroblasts expressing trk (trk-3T3). In each case MA-alpha 2M readily forms stable complexes with trk in vivo, whereas normal alpha 2M does not. Both

Subject

Humans; Male; Animals; Mice; Signal Transduction/drug effects/*physiology; Phosphorylation; PC12 Cells; Protein-Serine-Threonine Kinases/metabolism; Neurites/drug effects/*physiology; Nerve Growth Factors/*pharmacology; Adrenal Gland Neoplasms; alpha-Macroglobulins/isolation & purification/*metabolism/pharmacology; ErbB Receptors/isolation & purification/metabolism; Fibrinolysin/metabolism; Mitogen-Activated Protein Kinase 1; Pheochromocytoma; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/drug effects/isolation & purification/*metabolism; Receptor Protein-Tyrosine Kinases/drug effects/isolation & purification/*metabolism; Serotonin/*metabolism/pharmacology; Receptors; Receptor; Nerve Growth Factor/drug effects/isolation & purification/*metabolism; Platelet-Derived Growth Factor/isolation & purification/metabolism; trkA

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

5369–5376

Issue

7

Volume

269

Citation

Koo P H; Qiu W S, “Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction.,” NEOMED Bibliography Database, accessed April 15, 2021, https://neomed.omeka.net/items/show/5488.

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