Induction of a distinct morphology and signal transduction in TrkB/PC12 cells by nerve growth factor and brain-derived neurotrophic factor.
A clonal cell line stably expressing trkB (TrkB/ PC12) was established from rat pheochromocytoma PC12 cells. Brain-derived neurotrophic factor (BDNF), as well as nerve growth factor (NGF), stimulates neurite outgrowth in TrkB/PC12 cells. However, the morphology of BDNF-differentiated cells was clearly different from NGF-differentiated cells. BDNF treatment brought about longer and thicker neurites and induced a flattened soma and an increase in somatic size. This is not explained enough by the quantitative difference in the strength between TrkA and TrkB stimulation, because the level of BDNF-stimulated tyrosine phosphorylation of TrkB was similar to that of TrkA stimulated with NGF in PC12/TrkB cells. There was no difference in major tyrosine phosphorylated proteins induced by NGF and BDNF. Signal proteins such as phosphatidylinositol 3-kinase, phospholipase C-gamma 1, Shc, and mitogen-activated protein kinase seem to be involved in both TrkA- and TrkB-mediated signaling pathways. However, a tyrosine-phosphorylated 38-kDa protein (pp38) was detected in anti-pan-Trk immunoprecipitation only after NGF stimulation. Immunoprecipitation using three distinct anti-pan-Trk antibodies suggests that pp38 is not a fragment of TrkA. These data indicate that TrkA has a unique signal transduction pathway that is not stimulated through TrkB in TrkB/PC12 cells and suggest distinct functions among neurotrophin receptors.
Iwasaki
Y
Y
Bio-Organic Research Department, CIBA-GEIGY (Japan) Limited, Takarazuka, Japan.
Ishikawa
M
M
Okada
N
N
Koizumi
S
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D014443:Tyrosine