Nerve growth factor signal transduction in mature pig oligodendrocytes.
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 so-called 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-gamma1, 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-gamma1 is given by an NGF-induced increase of oligodendroglial [Ca2+]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.
Althaus
H H
HH
Max-Planck-Institute for Experimental Medicine, AG Neural Regeneration, Göttingen, Germany. althaus@mail.mpiem.gwdg.de
Hempel
R
R
Klöppner
S
S
Engel
J
J
Schmidt-Schultz
T
T
Kruska
L
L
Heumann
R
R
D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3; D026121:Indole Alkaloids; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine; D015854:Up-Regulation
D002227:Carbazoles; D026121:Indole Alkaloids; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C049985:staurosporine aglycone; C087857:protein kinase C gamma; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D002118:Calcium