PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts.
Although a large number of studies have been carried out on the diverse effects mediated by the common neurotrophin receptor p75(NTR), little is known about the molecular mechanisms by which p75(NTR) initiates intracellular signal transduction. We identified a variant of the beta catalytic subunit of cAMP-dependent protein kinase (PKACbeta) as a p75(NTR)-interacting protein, which phosphorylates p75(NTR) at Ser304. Intracellular cAMP in cerebellar neurons was accumulated transiently by ligand binding to p75(NTR). Activation of cAMP-PKA is required for translocation of p75(NTR) to lipid rafts, and for biochemical and biological activities of p75(NTR), such as inactivation of Rho and the neurite outgrowth. Proper recruitment of activated p75(NTR) to lipid rafts, structures that represent specialized signaling organelles, is of fundamental importance in determining p75(NTR) bioactivity.
Higuchi
Haruhisa
H
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-087, Japan.
Yamashita
Toshihide
T
Yoshikawa
Hideki
H
Tohyama
Masaya
M
D000595:Amino Acid Sequence; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D019208:Brain-Derived Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases