Contribution of receptor/G protein signaling to cell growth and transformation

While the effects of receptor/G protein systems on intermediary metabolism have been intensively studied, it has only recently been appreciated that G protein-coupled receptors and G proteins (heterotrimeric GTP-binding prote ins) play important roles in the regulation of cell growth, differentiation and even transformation. Naturally occurring mutations both in G protein-c oupled receptors and in G protein a-subunits lead to autonomous cell growth resulting in human disease. One mechanism to transduce mitogenic signals f rom the cell membrane to the nucleus is the engagement of the extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) casc ade. Multiple distinct signal transduction pathways have been characterized which link G proteins with the ERK cascade. Receptor and non-receptor tyro sine kinases play central roles in these pathways. Mitogenic signaling by r eceptor/G protein systems is realized as a complex interplay between signal s emanating from different classes of cell surface receptors. The character ization of receptor-, G protein- and tyrosine kinase-specific contributions to mitogenic signaling in a particular cell may ultimately allow for the r ational design and application of pharmaceuticals to treat diseases involvi ng uncontrolled cell proliferation.