Phosphorylation at Tyr-694 of Nogo-A by Src-family kinases.
Nogo-A is a neurite outgrowth inhibitor protein associated with myelin in the central nervous system. Unexpectedly, targeted disruption of Nogo-A in mice results in little or no improvement of axonal regeneration, suggesting that Nogo-A has other functions and/or receives complex regulations to exert its inhibitory functions. Here, we have found that Nogo-A becomes phosphorylated at Tyr-694 in the N-terminal region. The phosphorylation is mediated co-operatively by Src-family tyrosine kinases, which play many important roles in the nervous system. Levels of tyrosine phosphorylation of Nogo-A seem to be irrelevant to developmental stages of oligodendrocytes, and might be regulated by specific extracellular stimuli. Identification of tyrosine phosphorylation of Nogo-A will introduce an additional level of complexity into Nogo-A functions.
Yokoyama
Kazumasa
K
Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan.
Tezuka
Tohru
T
Hoshina
Naosuke
N
Nakazawa
Takanobu
T
Yamamoto
Tadashi
T
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002384:Catalysis; D006801:Humans; D051379:Mice; D009185:Myelin Proteins / Q000378:metabolism*; D000070798:Nogo Proteins; D010766:Phosphorylation; D011485:Protein Binding; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; D014443:Tyrosine; D019061:src-Family Kinases