Intracellular signaling pathways activated by neurotrophic factors.
Soluble and membrane embedded neurotrophic factors bind to specific receptors on responsive neurons and thereby initiate dramatic changes in the proliferation, differentiation, and survival of their target cells. Recent studies have elucidated many of the intracellular pathways by which neurotrophins and ciliary neurotrophic factor (CNTF) function to regulate gene expression and thereby achieve diverse biological responses. In this review we have focused particular attention on the importance of the Ras-MAP kinase pathway for neurotrophin signaling, and the role of the Jak-STAT pathway for CNTF signaling. Characterization of the enzymes, linker proteins, and transcription factors that are sequentially activated in response to neurotrophic factors has provided significant insight into the mechanisms by which these agents elicit specific biological responses during normal development and into the adaptive responses of mature neurons.
Segal
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Department of Neurology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Greenberg
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ME
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002450:Cell Communication; D020934:Ciliary Neurotrophic Factor; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D006801:Humans; D008959:Models, Neurological; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020794:Receptor Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018631:ras Proteins