Abstract
The four mammalian neurotrophins - NGF, BDNF, NT-3 and NT-4 - each bind and activate one or more of the Trk family of receptor tyrosine kinases. Through these receptors, neurotrophins activate many intracellular signaling pathways, including those controlled by Ras, the Cdc42/Rac/RhoG protein family, MAPK, PI3K and PLC-gamma, thereby affecting both development and function of the nervous system. During the past two years, several novel signaling pathways controlled by Trk receptors have been characterized, and it has become clear that membrane transport and sorting controls Trk-receptor-mediated signaling because key intermediates are localized to different membrane compartments. Three-dimensional structures of the Trk receptors, in one instance in association with a neurotrophin, have revealed the structural bases underlying specificity in neurotrophin signaling.
MeSH terms
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Animals
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Antigens, CD / physiology
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Apoptosis
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Cytoskeleton / physiology
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Cytoskeleton / ultrastructure
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Endocytosis
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Humans
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Isoenzymes / physiology
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology
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Mammals / physiology
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Mice
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Nerve Growth Factors / pharmacology
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Nerve Growth Factors / physiology*
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Nerve Tissue Proteins / physiology
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Neurons / physiology
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Organ Specificity
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PC12 Cells
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Phosphatidylinositol 3-Kinases / physiology
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Phospholipase C gamma
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Rats
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Receptors, Nerve Growth Factor / chemistry
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Receptors, Nerve Growth Factor / drug effects
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / physiology*
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Receptors, Tumor Necrosis Factor / physiology
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Receptors, Tumor Necrosis Factor, Type II
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Structure-Activity Relationship
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Type C Phospholipases / physiology
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ras Proteins / physiology
Substances
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Antigens, CD
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Isoenzymes
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Nerve Growth Factors
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Nerve Tissue Proteins
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type II
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Phosphatidylinositol 3-Kinases
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Type C Phospholipases
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Phospholipase C gamma
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ras Proteins