4at5: Difference between revisions
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{{STRUCTURE_4at5| PDB=4at5 | SCENE= }} | {{STRUCTURE_4at5| PDB=4at5 | SCENE= }} | ||
===CRYSTAL STRUCTURE OF TRKB KINASE DOMAIN IN COMPLEX WITH GW2580=== | |||
{{ABSTRACT_PUBMED_22902478}} | |||
== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/NTRK2_HUMAN NTRK2_HUMAN]] Defects in NTRK2 are the cause of obesity hyperphagia and developmental delay (OHPDD) [MIM:[http://omim.org/entry/613886 613886]]. OHPDD is a disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language.<ref>PMID:15494731</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/NTRK2_HUMAN NTRK2_HUMAN]] 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.<ref>PMID:15494731</ref> | |||
==About this Structure== | ==About this Structure== | ||
[[4at5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AT5 OCA]. | [[4at5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AT5 OCA]. | ||
==Reference== | |||
<references group="xtra"/><references/> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||