BIOL 304 - Chapter 14 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

key steps for signal transduction

1. release of the primary messenger

2. reception of the primary message by a receptor, a membrane proteins with intracellular and extracellular components

3. delivery of the message inside the cell by intracellular second messengers

4. activation of other molecules that directly alter the physiological response

5. termination of the signal

Seven-Transmembrane-Helix (7TM) Receptors

large class of cell-surface receptors

transmit diverse information initiated by hormones, neurotransmitters, odorants, and light

seven helices that span the membrane

agonist

ligands that activate receptors

how agonists change conformation

confirmation change on cytoplasmic side activates G protein

G protein activates adenylate cyclase —→ ATP to cAMP

signal pathway of epinephrine and beta-andregenic receptor

G protein and adenylate cyclase remain attached to the membrane

cAMP travels throughout the cell

G proteins

alpha, beta, and gamma subunits

alpha subunit bound to GDP

beta and gamma are anchored to membrane by covalently attached fatty acids

reacts with helices 5 and 6

when bound to receptor —→ alpha opens (GDP replaced by GTP)

adenylate cyclase

enzyme that converts ATP into cAMP

adenylate cyclase is activated by

binding of G protein 

GDP forming GTP

protein kinase A

protein that phosphorylates specific Ser and Thr residues in target proteins to alter their activity

role of cAMP regulation

PKA inactive in the absence of cAMP

binding of cAMP to the R chain frees C chains

troponin complex 

complex found in cardiac and skeletal muscle that blocks the ability of myosin to bind to actin

prevents muscle contraction

epinephrine binding promotes

cardiac muscle contraction

turn off of G protein

alpha subunits promote hydrolysis of bound GTP to GDP and Pi

resets G proteins

alpha-adregenic receptors

receptors that activate Gαq, a G protein that binds to and activates the enzyme phospholipase C when in its GTP form

bind epinephrine

how does calcium activate calmodulin?

calcium binding induces conformational changes in its EF hands

exposes hydrophobic surfaces that can bind proteins

the insulin receptor kinase is a

tyrosine kinase - catalyze the transfer of a phosphorylation group from ATP to hydroxyl group of Tyr

insulin binding results in

cross-phosphorylation and activation of the insulin receptor

protein kinase domains come together upon insulin binding

cross-phosphorylation of tyrosine residues

activates the kinase

Tyr residues are phosphorylated and cannot fit into active sites

opens active site

activated insulin-receptor kinase initiates

a kinase cascade

insulin-receptor substrates (IRS)

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

each IRS contains

four Tyr-X-X-Met sequences

When Tyr is phosphorylated, IRS molecules can act as adaptors and bring additional components of the signaling pathway together

phosphoinositide 3-kinases (PI3Ks)

specific lipid kinases that add a phosphoryl group to the 3-position of inositol in PIP2 to form phosphatidylinositol 3,4,5-trisphosphate (PIP3)

protein phosphatases

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

protein tyrosine phoshphatases

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