A signal transduction pathway involving IP3 and DG is shown in Figure 11-1. Agrowth factor or hormone binding to a cell-membrane receptor alters the receptor's conformation, which stimulates the dissociation of a neighboring trimeric G protein and a GDP attached to the α subunit of the G protein. The α subunit becomes active in the signal transduction pathway by dissociating from the β and γ subunits of the G protein and exchanging a molecule of GTP for GDP. The active G protein stimulates a membrane bound phospholipase C (PLC) that hydrolyzes the phosphatidylinositol 4',5'-bisphosphate (PIP2) in the membrane to DG and inositol 1',4',5'-triphosphate (IP3). IP3 binding to calcium ion pores opens these pores in the ER and the plasma membrane, allowing calcium ions to move along their concentration gradient from the ER and from the extracellular environment into the cytoplasm. Calcium ions and DG binding to inactive protein kinase C (PKC) causes PKC to become active. Activated PKC phosphorylates other protein kinases in signal transduction pathways, often activating them.
A second family of G proteins consist of a single subunit. These monomeric proteins are known as Ras proteins and are activated indirectly through autophosphorylation of membrane-bound tyrosine kinases and the regulatory proteins that interact with the phosphates (Figure 11-2). The relative amounts of active and inactive Ras are determined by guanine nucleotide release factors (GNRFs) and by GTPase-activating proteins (GAPs). Since these proteins promote the exchange of GTP for GDP, or GDP for GTP, respectfully, they affect Ras protein activity. Hydrolysis of GTP to GDP and Pi inhibits Ras. Some Ras proteins are negatively regulated by tumor suppressor proteins.
Ras proteins generally stimulate a cascade of protein kinases, whereas trimeric G proteins usually inhibit or stimulate enzymes such as adenylcyclase.
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