CHPT 14, BIOCHEM Signal Transduction

signal transduction pathways

chains of events that
convert molecular messages into a range of
physiological responses

transduction

the conversion of information of the
presence or concentration of a signal molecule into other
forms

adrenergic receptors

cell-surface proteins of two classes: α-
adrenergic receptors and β-adrenergic receptors

epinephrine (adrenaline)

hormone secreted by mammalian
adrenal glands in response to internal and external stressors
– exerts the fight-or-flight
response
– binds to β-adrenergic
receptors

seven-transmembrane-helix (7TM) receptors

large
class of cell-surface receptors
– transmit diverse information initiated by hormones,
neurotransmitters, odorants, and light
– nearly 1000 encoded in the human genome
– contain seven helices that span the membrane bilayer

agonists

ligands
that activate
receptors, helices 5+6 change the most upon binding

G-protein-coupled receptors (GPCRs)

another name for
7TM receptors because they signal through G proteins

adenylate cyclase

enzyme that converts ATP into
cAMP
– composed of 12 membrane-spanning helices
– the catalytic part is made of two cytoplasmic domains

protein kinase A (PKA)

protein that phosphorylates
specific Ser and Thr residues in target proteins to alter
their activity
– consists of two regulatory (R) two catalytic (C) chains
(R2C2)
– inactive in the absence of cAMP
– binding of cAMP to the R chains frees the C chains which
are catalytically activated when freed

troponin complex

complex
found in cardiac and skeletal
muscle that blocks the ability of
myosin to bind to actin
– prevents muscle contraction
– contains the protein troponin I
• In cardiac muscle cells, PKA
phosphorylates troponin I.
– Phosphorylation weakens
troponin binding to actin.
– Actin can interact with myosin

α-adrenergic receptors

receptors that activate Gαq, a G
protein that binds to and activates the enzyme
phospholipase C when in its GTP form
– expressed in the muscle cells that control pupil dilation and
line small blood vessels in skin
– bind epinephrine
– homologous to β-adrenergic receptors with very similar 3-
D structures

phospholipase C

catalyzes the cleavage of a
phosphatidylinositol 4,5-bisphosphate (PIP2), a cell
membrane phospholipid, into inositol 1,4,5-trisphosphate
(IP3) and diacylglycerol (DAG)

IP3

soluble second messenger that diffuses away from
the membrane
– causes the rapid release of Ca 2+ from the ER through
specific IP3-gated Ca2+–channel proteins

DAG

second messenger that remains in the plasma
membrane
– binds and activates protein kinase C (PKC)

protein kinase C (PKC)

protein kinase that
phosphorylates Ser and Thr residues in target proteins
– requires Ca 2+ to bind DAG

Ca 2+ participates in many
signaling processes
because

fleeting changes in Ca 2+
concentration are readily
detected.
– Ca 2+ can bind tightly to
proteins and induce
substantial structural
rearrangements.

EF hands

Ca 2+ -binding
motif that consists of a
helix, a loop, and a
second helix

calmodulin

a common
Ca 2+ sensor in eukaryotic
cells
– contains four EF-hand
motifs that can each
bind a single Ca 2+

insulin

peptide hormone
released in response to
increased blood-glucose
levels after a meal
– leads to the movements
of glucose transporters to
the surfaces of fat and
muscle cells

2 interchain disulfide
bonds.
– 1 intrachain disulfide
bond.

tyrosine kinases

catalyze the transfer of a phosphoryl
group from ATP to the hydroxyl group of Tyr

activation loop

unstructured region
containing a Tyr reside in the
active site that cannot be
phosphorylated because the
ATP-binding site is blocked

insulin-receptor substrates (IRSs)

substrates of the
insulin-receptor kinase
– examples: IRS-1 and IRS-2

pleckstrin homology domain

amino-terminal part of
IRSs that binds phosphoinositide
– acts with a phosphotyrosine-binding domain to anchor the
IRS protein to the insulin receptor and membrane

protein phosphatases

enzymes required to hydrolyze
phosphorylated proteins and return them to their initial
states

protein tyrosine phosphatases

remove phosphoryl
groups from Tyr residues on the insulin receptor and the
IRS adaptor proteins

protein serine phosphatases

remove phosphoryl groups
from activated protein kinases such as PKB

lipid phosphatases

enzymes required to remove
phosphoryl groups from inositol lipids such as PIP3