Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.

• GO:0007190 : activation of adenylate cyclase activity
• GO:0035584 : calcium-mediated signaling using intracellular calcium source
• GO:0021954 : central nervous system neuron development
• GO:0021987 : cerebral cortex development
• GO:0007631 : feeding behavior
• GO:0014047 : glutamate secretion
• GO:0007612 : learning
• GO:0060291 : long-term synaptic potentiation
• GO:0042490 : mechanoreceptor differentiation
• GO:2000811 : negative regulation of anoikis
• GO:0043524 : negative regulation of neuron apoptotic process
• GO:0048011 : nerve growth factor receptor signaling pathway
• GO:0001764 : neuron migration
• GO:0048709 : oligodendrocyte differentiation
• GO:0048935 : peripheral nervous system neuron development
• GO:0050772 : positive regulation of axonogenesis
• GO:0008284 : positive regulation of cell proliferation
• GO:0010628 : positive regulation of gene expression
• GO:0043410 : positive regulation of MAPK cascade
• GO:0010976 : positive regulation of neuron projection development
• GO:0014068 : positive regulation of phosphatidylinositol 3-kinase cascade
• GO:0051968 : positive regulation of synaptic transmission, glutamatergic
• GO:0046777 : protein autophosphorylation
• GO:0050773 : regulation of dendrite development
• GO:0046928 : regulation of neurotransmitter secretion
• GO:0051896 : regulation of protein kinase B signaling cascade
• GO:0032314 : regulation of Rac GTPase activity
• GO:0046548 : retinal rod cell development
• GO:0001570 : vasculogenesis

Source: The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet.. May 2000;25(1):25-9.
World Wide Web URL: http://www.geneontology.org/

• OMIM:600456 : Obesity, hyperphagia, and developmental delay (OMIM:613886 )

Source: Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), May, 2012.
World Wide Web URL: http://omim.org/