Figure 1

Cartoon schematic of important regulatory structures in Kv1.3 ion channel, Neurotrophin receptor tyrosine kinase B (TrkB), and the adaptor proteins, growth factor receptor binding protein (Grb10) and neuronal and Src homology and collagen (nShc). Brain-derived neurotrophic factor (BDNF) binds to TrkB, which induces receptor dimerization, autophosphorylation of multiple Y residues in the β chains, and subsequent phosphorylation of the Kv1.3 downstream substrate. Site-directed mutagenesis has been used to map the molecular targets for phosphorylation of the channel via activation of insulin receptor kinase (+), Src kinase (*), or TrkB (#). ● = Tyrosine (Y) to phenylalanine (F) point mutations made to eliminate various phosphorylation recognition motifs. Proline-rich PXXP domains in channel and adaptors as noted that are known to bind to SH3- domain containing proteins. Note SH2 domains of Grb10 and nShc that recognize Y-phosphorylated residues in protein partners. Shc binding site on TrkB (Y⁴⁹⁰) is also noted (TrkBShc-). SH3 = Src homology 3 domain, SH2 = Src homology 2 domain, PTB = protein tyrosine binding, PH = pleckstrin homology domain, BPS = binding phosphorylated substrate, PLC = phospholipase C, β = beta subunit.