Signal Transduction

Cascade is what

Series of events where small signal is amplified

Cascade steps

1) A single receptor can interact with multiple tranducer molecules

2) A tranducer can interact with multiple effector enzymes

3) Second messengers can activate many kinases

4) Kinases can phosphorylate many target molecules

Signal cascade to break down glycogen step 1

Primary messenger: Hormone signals to breakdown glycogen

Signal cascade to break down glycogen step 2

Receptor binds hormone. Signal is transmitted into the cell

Signal cascade to break down glycogen step 3

Signal Transducer

Signal cascade to break down glycogen step 4

Effector enzyme

G proteins inactive when

bound to GDP

G proteins active when

bound to GTP

G protein turning signal on

Activation occurs when the G-GDP interacts with a hormone receptor complex activating the G protein by:

1) replacement of GDP with GTP

2) conformational change in a subunit

3) dissociation of b and g subunits

G-GTP now propagates a signal by interacting with an effector protein

G protein turning signal off

The a subunit slowly hydrolyzes GTP to GDP, dissociating from the effector protein.

G-GDP associates with b and g subunits and is ready for another cycle of activation

Adenylyl Cyclase Activation pathway

Hormone binds to and activates a stimulatory receptor (Rs).

Rs activates a stimulatory G protein (Gas)-GTP.

Gas-GTP activates adenylyl cyclase which synthesizes cAMP(5’,3’ AMP).

cAMP binds protein kinase A (PKA); this releases C subunits from R subunits and PKA is activated.

PKA phosphorylates target proteins (transcription factors) at Ser Thr, activating them.

Adenylyl Cyclase inhibitory pathway

An inhibitory hormone binds a receptor Ri, which activates a (Gia) by stimulating exchange of GTP in place of GDP.

Gia -GTP inhibits adenylyl cyclase, and the subsequent activation steps are reversed.

cAMP Synthesis turning the signal on

Adenylyl cyclase: cyclizes ATP to cAMP

cAMP Synthesis turning the signal off

Cyclic nucleotide phosphodiesterase: inactivates cAMP producing AMP

cAMP activates…

protein kinase A (PKA)

Inositol-phospholipid signaling pathway step 1

A receptor R binds a ligand and this activates a G protein Gq.

Inositol-phospholipid signaling pathway step 2

Gq activates a membrane-bound phospholipase C enzyme (PLC).

Inositol-phospholipid signaling pathway step 3

PLC hydrolyzes phosphatidylinositol 4,5 bisphosphate (PIP2).

Inositol-phospholipid signaling pathway step 4

The products of that hydrolysis are IP3 and DAG

Inositol-phospholipid signaling pathway step 5

IP3 diffuses to endoplasmic reticulum where it binds to Ca+2 channels and this opens the channels, transiently allowing more Ca+2 into the cell.

Inositol-phospholipid signaling pathway step 6

Ca+2 activates Ca+2- dependent protein kinases.

Activity of Ca 2+ and DAG

Ca2+ and DAG activate Protein Kinase C (C for Calcium)

Ca2+ activates Calmodulin (CaM) dependent Protein Kinase

Receptor Tyr kinase is what type of receptor

Insulin receptor

Receptor Tyr kinase works by

The tyrosine kinase domains of the receptor in the inactive state are separated

Upon ligand binding, a conformational change brings them together forming a dimer

When kinases are close together inside cell there is autophosphorylation.

insulin tyrosine receptor kinase pathway

the insulin receptor phosphorylates insulin receptor substrates (IRSs); these activate a number of kinases involved in nutrient utilization.

One of the IRSs activates (PIP2) kinase.

PI kinase phosphorylates PIP2 to PIP3.

PIP3 activates PIP3-dependent protein kinases