Scientific Background: | TRKA is a member of the trk proto-oncogene family and encodes a 140 kilodalton, membrane-spanning protein tyrosine kinase that is the functional receptor for nerve growth factor (NGF). NGF elicits the rapid phosphorylation of gp140trk on tyrosine residues leading to increased c-Fos expression, DNA synthesis and morphologic transformation. The major pathways activated by the Trk receptors are Ras, Rac, PI 3-kinase, PLC-γ1 and their downstream effectors. These include Ras stimulation of MAP kinase cascades, PI 3-kinase stimulation of Akt and PLC-γ1-dependent generation of IP3 and diacylglycerol (DAG) that results in mobilization of Ca2+ and activation of Ca2+ and DAG-regulated protein kinases. |