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