Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of TrkA.
GM1 enhances nerve growth factor (NGF)-stimulated neuritogenesis and prevents apoptotic death of PC12 cells; both may be due to enhancement of TrkA dimerization. In this study, we examined the effect of GM1 on NGF-induced TrkA dimerization in Trk-PC12 (6-24) cells. NGF increased tyrosine phosphorylation of the 140-kDa protein (TrkA monomer), and preincubation with GM1 potentiated this effect. Adding the protein cross-linker bis(sulfosuccinimidyl) suberate with NGF resulted in the appearance of two major bands (220 and 330 kDa) when probed with antibodies against TrkA or phosphotyrosine, and GM1 also enhanced this effect. We interpret the 330-kDa band as being a homodimer of TrkA. The identity of the 220-kDa band is still not certain but may consist of a posttranslationally modified form of TrkA. Our results suggest that GM1 is augmenting the effects of NGF on PC12 cells by enhancing the dimerization and activation of the TrkA receptor.
Farooqui
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T
Department of Pathology, Ohio State University, Columbus 43210, U.S.A.
Franklin
T
T
Pearl
D K
DK
Yates
A J
AJ
D000818:Animals; D003432:Cross-Linking Reagents / Q000494:pharmacology; D019281:Dimerization; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D003432:Cross-Linking Reagents; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D013388:Succinimides; D005677:G(M1) Ganglioside; D014443:Tyrosine; C035760:bis(sulfosuccinimidyl)suberate; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA