12
U N I T 1
Cell and Tissue Function
which recognizes a specific ligand or first messenger. Upon
ligand-binding, they all undergo conformational changes
that activate the G protein found on the cytoplasmic side
of the cell membrane (Fig. 1-9). All G proteins incorpo-
rate the
guanosine triphosphatase (GTPase) cycle
, which
functions as a molecular switch that exists in two states:
an activated (on) state and an inactivated (off) state.
Receptor activation causes the
α
subunit to dissociate
from the receptor and the
β
and
γ
subunits and transmit
the signal from the first messenger to a membrane-bound
intermediate called an
effector
. Often, the effector is an
enzyme that converts an inactive precursor molecule into
a second messenger, which diffuses into the cytoplasm and
carries the signal beyond the cell membrane. One com-
mon effector is the enzyme
adenylyl cyclase
, which con-
verts the precursor ATP to the second messenger cAMP,
transferring the two phosphate groups to other proteins.
This transfer changes the conformation and function of
these proteins. Such changes eventually produce the cell
response initiated by the first messenger, whether it is a
secretion, muscle contraction or relaxation, or change in
metabolism. Sometimes it is the opening of membrane
channels involved in calcium or potassium influx.
Enzyme-Linked Receptors.
Like G protein–linked
receptors, enzyme-linked receptors are transmembrane
Integration of Cell Function
Within a complex organism, such as a human being, dif-
ferent organs, tissues, and individual cell types develop spe-
cialized functions and needs. Yet each cell must contribute
to the integrated life process as the body grows, differenti-
ates, and adapts to changing conditions. Such integration
requires that cells have the ability to communicate with one
another, transport substances between their intracellular
and extracellular environments, and generate and respond
to changes in the electrical charge of membrane potentials.
Cell Signaling and Communication
Mechanisms
Signaling systems consist of receptors that reside either
on the cell membrane (surface receptors) or within the
cells (intracellular receptors). Receptors are activated by
a variety of chemical messengers including neurotrans-
mitters, hormones, growth factors, and other chemical
messengers, as well as signaling proteins called
cyto-
kines
and
lipids
. Some lipid-soluble chemical messengers
move through the membrane and bind to cytoplasmic
or nuclear receptors to exert their physiologic effects.
Signaling systems often rely on the intermediary activity
of a separate class of membrane-bound regulatory pro-
teins to convert extracellular signals, or first messengers,
into intracellular signals, or second messengers, such
as a unique form of adenosine monophosphate called
cyclic adenosine monophosphate
(cAMP). Many mol-
ecules involved in signal transduction within cells are
enzymes and other proteins. Some of the enzymes are
protein kinases that catalyze the phosphorylation of
proteins, thereby changing their activity and function.
Cell Surface Receptors
Each cell type in the body contains numerous receptor
proteins, which as a set may characterize the cell type,
that enable it to respond to a complementary set of
ligands (i.e., molecules with a high affinity for a recep-
tor) or signaling molecules in a specific, preprogrammed
way. These receptors, which span the cell membrane,
relay information to a series of intracellular interme-
diates that eventually pass the signal to its final des-
tination. There are three major classes of cell surface
receptor proteins: G protein–linked receptors, enzyme-
linked receptors, and ion channel–linked receptors.
G Protein–Linked Receptors.
G protein–linked recep-
tors mediate cellular responses for numerous types of
first messengers through regulatory proteins called
G
proteins
that bind to guanine nucleotides such as guanine
diphosphate (GDP) and guanine triphosphate (GTP).
With more than 1000 members, G protein–linked recep-
tors are the largest family of cell surface receptors.
Although there are differences among the G protein–
linked receptors, all share a number of features. They all
have a ligand-binding extracellular receptor component,
ATP
cAMP
Receptor
G protein
(Transducer)
Amplifier Enzyme
Hormone
(First messenger)
Phosphorylated
precursor
Second messenger
Intracellular effector
Cell response
Extracellular
fluid
Intracellular
fluid
Adenyl cyclase
FIGURE 1-9.
Activation of a G-protein-linked receptor and
production of cyclic adenosine monophosphate (cAMP).
Binding of a hormone (the first messenger) causes the
activated receptor to interact with the inactive, guanine
diphosphate (GDP)-bound G protein.This results in activation
of the G protein and dissociation of the G protein
α
,
β
, and
γ
subunits.The activated
α
subunit of the G protein can then
interact with and activate the membrane protein adenyl cyclase
to catalyze the conversion of adenosine triphosphate (ATP)
to the second messenger cAMP. The second messenger then
activates an internal effector, which leads to the cell response.
(
text continued from page 9
)
