A function–structure model for NGF‐activated TRK

摘要: Mechanisms regulating transit of receptor tyrosine kinases (RTKs) from inactive to active states are incompletely described, but require autophosphorylation tyrosine(s) within a kinase domain ‘activation loop’. Here, we employ functional biological assays with mutated TRK receptors assess ‘switch’ model for RTK activation. In this model: (i) ligand binding stimulates activation loop phosphorylation; (ii) these phosphotyrosines form specific charge pairs nearby basic residues; and (iii) the stabilize functionally conformation in which is restrained blocking access catalytic core. Our findings both support identify residues that each three phosphotyrosines.