Receptor Tyrosine Kinases Specific Outcomes from General Signals

tion of MAPK, induces neuronal differentiation in these cells, while EGF, which induces a much shorter MAPK Understanding how groups of initially equivalent cells activation, induces proliferation (Marshall, 1995). Con-develop into complex tissues containing many cell types sistent with the idea that this difference in signal perdu-is an important goal for biologists. In recent years, it rance determines the nature of the response, experi-has become increasingly clear that the developmental mental manipulations that lengthen the response to EGF fate of individual cells is often established by activating can cause EGF signaling to induce neuronal differentia-transmembrane receptors of the Receptor Tyrosine Ki-tion. Similarly, studies of signaling by the Drosophila nase (RTK) family. RTKs dimerize in response to binding Torso RTK, which is required for specification of the their specific ligand(s) (van der Geer et al., 1994). Dimer-termini of the embryo, have suggested that the strength ization leads to autophosphorylation of the RTK as well of signal determines which transcriptional targets of the as the phosphorylation of other signaling molecules on Torso pathway are induced (Greenwood and Struhl, specific tyrosine residues. As a result of these phosphor-1997). In this case, strong activation of Ras induces both ylation events, a number of intracellular signal transduc-huckebein and tailless expression while weaker Torso tion cascades are initiated. Perhaps the most important activation can only induce tailless expression. An exam-consequence of RTK activation is an increase in the ple of a qualitative difference in signaling pathways has activity of Ras, and thus, MAP kinase (MAPK). Activated come from studies of the C. elegans Let-23 RTK, which MAPK can modulate the activity of various transcription appears to use distinct signaling pathways in different factors and other cellular proteins. In this model, the primary reason for the existence of activation of MAPK is thought to promote transcription so many ligands and RTKs is to allow the temporally by causing a switch of activated Pointed P2 for Yan at and spatially appropriate activation of general RTK intra-Ets sites. It is important to note that Pointed P2 and Yan cellular signaling pathways rather than to allow for differ-are thought to be regulated downstream of all RTKs in ent kinds of RTK signaling. Support for this model comes the fly. from studies showing that the expression of a constitu-One theme that has emerged from studies of RTK tively activated Ras protein can compensate for the ab-action is that different RTKs stimulate …