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PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts
Author(s) -
Higuchi Haruhisa,
Yamashita Toshihide,
Yoshikawa Hideki,
Tohyama Masaya
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg177
Subject(s) - biology , lipid raft , microbiology and biotechnology , neurite , intracellular , signal transduction , low affinity nerve growth factor receptor , phosphorylation , protein kinase a , neurotrophin , kinase , receptor , biochemistry , in vitro
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 β catalytic subunit of cAMP‐dependent protein kinase (PKACβ) 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.