The signaling molecules that activate receptor tyrosine kinases are soluble or membrane-bound peptide or protein hormones, including many that were initially identified as growth factors for specific types of cells. Many of these RTK ligands, such as nerve growth factor (NGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF), stimulate proliferation and differentiation of specific cell types. Others, such as insulin, regulate expression of multiple genes that control sugar and lipid metabolism in liver, muscle, and adipose (fat) cells. Many RTKs and their ligands were identified in studies of human cancers associated with mutant forms of growth-factor receptors that stimulate proliferation even in the absence of the growth factor. The mutation “tricks” the receptor into behaving as though the ligand is present at all times, so the receptor is constantly in an active state (constitutively active; see Chapter 24). Other RTKs have been uncovered during analysis of developmental mutations that lead to blocks in differentiation of specific cell types in C. elegans, Drosophila, and the mouse.