Distinctive features of Trk neurotrophin receptor transactivation by G protein-coupled receptors.
Ligands for G protein-coupled receptors (GPCR) are capable of activating mitogenic receptor tyrosine kinases, in addition to the mitogen-activated protein (MAP) kinase signaling pathway and classic G protein-dependent signaling pathways involving adenylyl cyclase and phospholipase. For example, receptors for epidermal growth factor (EGF), insulin-like growth-1 and platelet-derived growth factor and can be transactivated through G protein-coupled receptors. Neurotrophins, such as NGF, BDNF and NT-3 also utilize receptor tyrosine kinases, namely TrkA, TrkB and TrkC. Recently, it has been shown that activation of Trk receptor tyrosine kinases can also occur via a G protein-coupled receptor mechanism, without involvement of neurotrophins. Adenosine and adenosine agonists can activate Trk receptor phosphorylation specifically through the seven transmembrane spanning adenosine 2A (A2A) receptor. Several features of Trk receptor transactivation are noteworthy and differ significantly from other transactivation events. Trk receptor transactivation is slower and results in a selective increase in activated Akt. Unlike the biological actions of other tyrosine kinase receptors, increased Trk receptor activity by adenosine resulted in increased cell survival. This article will discuss potential mechanisms by which adenosine can activate trophic responses through Trk tyrosine kinase receptors.
Lee
Francis S
FS
Department of Psychiatry, Weill Medical College of Cornell University, New York, NY 10021, USA.
Rajagopal
Rithwick
R
Chao
Moses V
MV
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000378:metabolism; D011485:Protein Binding; D020917:Receptor, trkA / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
D008024:Ligands; D009414:Nerve Growth Factors; D066246:ErbB Receptors; D020917:Receptor, trkA; D019204:GTP-Binding Proteins