Cell Bio Exam 3 Signaling Examples

G protein coupled examples

•Seven-pass transmembrane receptors

Adrenaline receptor and acetylcholine receptor

G protein coupled activation

binding of extracellular signal mol to receptor changes conformation of G protein,

allowing GDP to change to GTP

activates Beta and Alpha subunit of G protein

G coupled deactivation

alpha subunit is activated and bound to target protein

the alpha subunit hydrolysis its GTP back to GDP and removes from target

inactive alpha subunit reassembles with beta unit to reform an inactive g protein

Acetylcholine receptor on heart cells

-binding of ACH to its GPCReceptor and activates G protein

-the activated Beta unit opens a K+ channel in the membrane (slow heart rate)

-Inactivate by hydrolysis of GTP and closing K+ channels

Adrenaline receptor

-adrenaline activates gpcreceptor that turns on G protein and activates adenylyl cylase 

-boost production of cyclic AMP which activates PKA, which phosphyrlates and activates another kinsae

-kinase phosphorylates (activates) glycogen phosphorylase (which breaks down glycogen)

-PKA also phosphrylates and inactivates glycogen synthase

happens fast 

additional info abt active pKA

activate transcription factors that regulate such processes as memory in the brain and hormone synthesis in endocrine cells

Enzyme-coupled examples 

•Cytoplasmic domain acts as enzyme or associates with one

Receptor tyrosine kinases (RTKs) (largest class)
(a) MAP-kinase signaling pathway

(b) PI3-kinase/Akt signaling pathway

RTKs

•Examples- EGFR, VEGFR, nerve growth factor, etc.

•Most mediate signals through the GTPase called Ras (growth)

•Akt is another popular RTK-induced pathway (survival)

turning off RTKs

How do we turn them off?

  1) protein tyrosine phosphatases (removes phosphates that were added to tyrosines) 

  2) endocytosis (dragged into interior of cell in a vesicle then destroyed by lysozomes

RTK activation

• signal molecule to extracellular causes two receptors to form dimer

• activates kinase to phsophorylate tyosines on the receptor tails

• each phosphorylized tyosine is a docking site for different intracellular signal protein

  • activation of intracellular signal pathway

RTK activation of Ras-MAP K

-adaptor protein docks to an activated RTK tyosine

-recuits Ras GEF that stimulates exchange from GDP to GTP in Ras protein (G protein)

-activated RAS can now stimulate signaling pathway 

Ras-MAP-kinase signaling cascade

activated Ras protein activares 3 kinase signaling pathway

-final kinase (MAP Kinase) phsophroylates multiple effector proteins that affect protein activity/gene expression

PI-3-Kinase—AKT signaling pathway

Activated RTK recuits and activates PI 3- Kinase then phosphorylattes inositol phospholipid  

- phosphorylated inositol phospholipid attracts intravellular signaling protein (AKT) and activates it 

-AKT is released from  membrane and phosphorylates signaloing pathway

Activation of Akt promotes cell survival (1)

-phosphorylizes and inactivating BAD protein (promotes apoptosis by binding and inhibiting a protein (Bcl2) that supresses apoptosis)

-when Bad is phosphorylyzed by Akt, it releases (Bcl2) now blocking apoptosis (promoting cell survival)

Activation of Akt promotes cell survival (2)

-active AKT indirectly activates Tor

Tor stimulates protein synthesis and inhibits degradation of proteins

= cell growth

complexity of cell receptors

-individual receptors can “talk” to multiple pathways

- messages can be sent at the same time, and may overlap

cell surface receptors make..

good targets for drugs

What are some things that signals tell cells to do?

alter metabolism

altered cell/shape movement

altered gene expression