Lecture 16: Cell Signaling pt. 2

four classes of cell-surface receptors

• ion-channel linked receptor

• G-protein-linked receptor

• enzyme-linked receptor

• receptor coupled to transcription factors

ion-channel linked receptor

• converts chemical signals into electrical signals

• specialty of the nervous system and other electrically excitable cells, such as muscle

G-protein-linked receptor

• largest family of cell surface receptors

• large diversity of extracellular signal molecules

• highly conserved from yeast to humans

enzyme-linked receptor

receptor coupled to transcription factors

G-protein-linked receptor structure

seven-pass transmembrane receptor protein

G-protein-linked receptor function

activates G proteins

G protein function

protein targets ion channels or membrane bound enzymes

G protein structure

α, β and γ subunits

activated G protein

• separates into α and βγ subunits

• alpha subunit is bound to GTP

inactivated G protein

• heterotrimic

adenylate cyclase

synthesizes cyclic AMP in response to G-protein signaling

what does activated GTP bound G Alpha subunit cause?

• activate target protein adenylate cyclase to increase cAMP level

• activates another target protein phospholipase C

where does cAMP bind?

regulatory subunit of protein kinase A to activate protein kinase A

how is protein kinase A activated?

cAMP binds to regulatory subunit of protein kinase A to activate protein kinase A

major function of cAMP in animal cells

secondary messenger to activate protein kinase A

function of phospholipase C

split PIP2 to IP3 and DAG

IP3

opens Ca2+ channel in ER

what molecules activate protein kinase C?

diacylglycerol (DAG) and calcium

how does protein kinase A activates genes?

• binding cAMP to its regulatory subunits

• release its catalytic subunits,

• enter nucleus and phosphorylate CREB (transcription factor)

how does protein kinase A regulate glycogen metabolism?

phosphorylates phosphorylase kinase and glycogen synthase

cholera toxin

• modifies the a subunit of a G protein so that it cannot hydrolyze its bound GTP

• increased Gαs activation leads to increased adenylate cyclase activity, which increases cAMP concentration

• result: rapid fluid loss from intestine

cGMP

• second messenger

• converts visual signal to nerve impulses

• relaxes smooth muscles by dilating blood vessels