Five basic mechanisms of transmembrane signaling are well understood. Each uses a different strategy to circumvent the barrier posed by the lipid bilayer of the plasma membrane. These strategies use: a lipid-soluble ligand that crosses the membrane and acts on an intracellular receptor. a transmembrane receptor protein whose intracellular enzymatic activity is allosterically regulated by a ligand that binds to a site on the protein's extracellular domain. a transmembrane receptor that binds and stimulates a protein tyrosine kinase. a ligand gated transmembrane ion channel that can be induced to open or close by the binding of a ligand. a transmembrane receptor protein that stimulates a GTP-binding signal transducer protein (G protein), which in turn modulates production of an intracellular second messenger. Known transmembrane signaling mechanisms:1: A lipid-soluble chemical signal crosses the plasma membrane and acts on an intracellular receptor (which may be an enzyme or a regulator of gene transcription); 2: the signal binds to the extracellular domain of a transmembrane protein, thereby activating an enzymatic activity of its cytoplasmic domain; 3: the signal binds to the extracellular domain of a transmembrane receptor bound to a separate protein tyrosine kinase, which it activates; 4: the signal binds to and directly regulates the opening of an ion channel; 5: the signal binds to a cell-s urface receptor linked to an effector enzyme by a G protein. (A, C, substrates; B, D, products; R, receptor; G, G protein; E, effector ; Y, tyrosine; P, phosphate.) Receptor Ligand Ligand gated receptor Insulin, EGF, PDGF, ANP Nuclear receptor Fenofibrate. Gemfibrizol G protein coupled receptor Catecholamine Enzymatic receptor