TrkA NGF receptor plays a role in the modulation of p75NTR expression.
The cellular response to nerve growth factor (NGF) is mediated by two structurally unrelated receptors, TrkA and p75 neurotrophin receptor (p75NTR), which have been shown to interact resulting in reciprocal modulation of function. In this study, we have examined the modulation of p75NTR protein expression by specific TrkA autophosphorylation sites in the presence or absence of NGF. We have used cell lines derived from PC12 cells that express either no endogenous TrkA (PC12nnr5) or TrkA receptors mutated via site-directed mutagenesis to abrogate individual tyrosine autophosphorylation sites on the cytoplasmic tail (Y490F, Y785F and Y490/785F). Results indicate that in the absence of TrkA in PC12nnr5 cells there is reduced constitutive p75NTR expression, which can be restored to different degrees by transfection of the Y490F TrkA or the Y490/785F TrkA, but not by transfection of the Y785F TrkA. In addition, the expression of p75NTR was upregulated in the presence of NGF in the parental and Y490F cell lines only. Together these results indicate a role for the individual tyrosine autophosphorylation sites of TrkA in regulating p75NTR expression.
Rankin
Sherri L
SL
Division of Basic Medical Sciences-M5352, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Phillip Drive, St. John's, Nfld., Canada A1B 3V6.
Guy
Clifford S
CS
Mearow
Karen M
KM
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D009154:Mutation / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection / Q000379:methods
D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA