|Figure 11-1 A signal transduction pathway.
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
) in the membrane to DG and inositol
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.
|Figure 11-2 Regulation of the ras gene product
by (a) GAPs and (b) GNRFs.
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.