Comparative Study the Activation of Post-Receptor Signal Pathways by Dipeptide Mimetics of the 4th Loop of Rat and Human NGF in the Mouse Hippocampal Cell Line HT-22

Using mouse hippocampal cell cultures, the activation of the TrkA receptor, Akt 1/2/3, and Erk 1/2 kinases by GK-2 and GK-2(h)—dipeptide mimetics of the fourth loop of rat and human NGF, respectively—was examined in a comparative study. The findings suggest that both of these mimetics, like NGF, activate a specific neurotrophic TrkA receptor. However, the pattern of receptor activation in HT-22 cells under the action of GK-2 and GK-2(h) was different. GK-2 induced a more pronounced and prolonged activation of the receptor than GK-2(h). Both mimetics did not activate Erk 1/2. In studying the activation of Akt 1/2/3 kinases, we identified differences in the effects of these peptides. GK-2 induces longer-lasting phosphorylation of Akt 1/2/3 kinases in NT-22 mouse hippocampal cell cultures compared to GK-2(h).