Intracellular receptors include transcription factors that are activated by lipid-soluble ligands that easily transit plasma membranes. Examples include vitamin D and steroid hormones, which activate nuclear hormone receptors. In other settings, a small and/or nonpolar signaling ligand can diffuse into adjacent cells. Such is the case for nitric oxide (NO), through which endothelial cells regulate intravascular pressure. NO is generated by an activated endothelial cell and then diffuses into adjacent vascular smooth muscle cells; there it activates guanylyl cyclase to generate cyclic GMP, an intracellular second signal that causes smooth muscle relaxation.
Cell-surface receptors are generally transmembrane proteins with extracellular domains that bind activating ligands. Depending on the receptor, ligand binding may (1) open ion channels (typically at the synapse between electrically excitable cells), (2) activate an associated GTP-binding regulatory protein (G protein), (3) activate an endogenous or associated enzyme, often a tyrosine kinase, or (4) trigger a proteolytic event or a change in protein binding or stability that activates a latent transcription factor. Activities (2) and (3) are associated with growth factor signaling pathways that drive cell proliferation, whereas activity (4) is a common feature of multiple pathways (e.g., Notch, Wnt, and Hedgehog) that regulate normal development. Understandably, signals transduced by cell surface receptors are often deranged in developmental disorders and in cancers.
Binding of a ligand to a cell surface receptor mediates signaling by inducing clustering of the receptor (receptor http://ebooksmedicine.net
Transcription of nuclear Transcription of Transcription A Nucleus hormone target gene notch target gene
Inactivation by hydrolysis of GTP
Activation of transcription