Neudesin, a novel secreted protein with a unique primary structure and neurotrophic activity.
We identified a novel secreted protein and named it neudesin. Mouse neudesin of 171 amino acids is unique with no primary structural similarity to any known proteins. The neudesin protein produced in cultured cells was secreted efficiently into the culture medium. Mouse neudesin mRNA was expressed abundantly in the developing brain and spinal cord in embryos, but was expressed widely in postnatal tissues including brain, heart, lung, and kidney. Mouse neudesin mRNA was expressed in neurons but not glial cells of the brain. The protein exhibited significant neurotrophic activity in primary cultured mouse neurons but not mitogenic activity in primary cultured mouse astrocytes. Neudesin activated the mitogen-activated protein (MAP) and phosphatidylinositol-3 (PI-3) kinase pathways. The activity of neudesin was inhibited by the inhibitor pertussis toxin for Gi/Go-protein but not by inhibitors for receptor tyrosine kinases. These results indicated that the activity was mediated via the activation of the MAP and PI-3 kinase pathways, potentially by the activation of a Gi/Go-protein-coupled receptor. Human neudesin of 172 amino acids with high similarity ( approximately 91% identity) to mouse neudesin was also identified. The human neudesin gene was mapped to chromosome 1p33. The identification of neudesin, a novel secreted protein with a unique primary structure and neurotrophic activity, will provide new insights into the development and maintenance of neuron
Kimura
Ikuo
I
Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto, Japan.
Yoshioka
Masazumi
M
Konishi
Morichika
M
Miyake
Ayumi
A
Itoh
Nobuyuki
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C500818:NENF protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C500817:neudesin protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go