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Nerve growth factor signal transduction in mature pig oligodendrocytes

✍ Scribed by H.H. Althaus; R. Hempel; S. Klöppner; J. Engel; T. Schmidt-Schultz; L. Kruska; R. Heumann

Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
350 KB
Volume
50
Category
Article
ISSN
0360-4012

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✦ Synopsis

It has previously been shown that nerve growth factor (NGF) is of functional significance for mature pig oligodendrocytes (OLs) in culture. The present data give evidence for the expression of TrkA, the so-called high-affinity NGF receptor, and of p75NTR, the socalled low-affinity NGF receptor. TrkA is upregulated during culturing, in contrast to the p75 receptor. Exposure of OLs to NGF induces an autophosphorylation of TrkA via its intrinsic tyrosine kinase. K-252a inhibits the TrkA autophosphorylation, which reduces the OL process formation to control levels. To the tyrosine-phosphorylated sites of TrkA several proteins, such as phospholipase C-␥1, the adaptor protein SHC, the phosphotyrosine phosphatase SH-PTP2 (SYP) associate via their SH2 phosphotase SH-PTP2 domain. The association of SHC to TrkA is shown by co-immunoprecipitation. Indirect evidence for a possible activation of PLC-␥1 is given by an NGF-induced increase of oligodendroglial [Ca 2؉ ] i . Downstream from TrkA, a mitogen-activated protein kinase cascade, which includes Erk1 and Erk2, is operating. An in-gel myelin basic protein kinase assay revealed that NGF activates predominantly Erk1. Finally, it is shown that NGF stimulates expression of c-fos.

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