PathwayStep5195 PathwayStep5194 TRKA activation by adenosine A2a receptor TRKA activation by PACAP type 1 receptor NGF-independant TRKA activation Authored: Nasi, S, Annibali, D, 2006-10-10 09:07:07 Edited: Jassal, B, 2006-10-10 09:20:18 GENE ONTOLOGYGO:0007190 Pubmed16805430 Reactome Database ID Release 43187024 Reactome, http://www.reactome.org ReactomeREACT_11046 TRK receptors can also be activated by at least two G-protein-coupled receptors (GPCR), the adenosine A2a receptor and the PACAP type I receptor, without involvement of neurotrophins. Activity of both receptors is mediated by G proteins that activate adenyl cyclase. How this leads to TRKA activation has not been fully elucidated, although a SRC-family tyrosine kinase and intracellular Ca2+ appear to play a role. TRKA activation through GPCRs occurs with slow kinetics (over 1 hr adenosine or PACAP treatment is required) in an intracellular location (probably the Golgi apparatus), and requires transcriptional and protein synthesis events that may influence the processing and activation of the receptors. GPCR-mediated transactivation of TRK receptors causes the preferential activation of AKT versus ERKs. This leads to a cell survival response.