3 - GS, GI, AND GQ PATHWAYS

Gs pathway components

1. Gs alpha

2. Adenylate cyclase

3. cAMP

4. Protein Kinase A (PKA)

Gs pathway Sequence of activation

Ligand binds receptor → Gsα binds GTP → activates adenylate cyclase → increases cAMP → activates PKA → phosphorylates proteins

Gs final cellular response

Activation of enzymes via PKA-mediated phosphorylation

Gi pathway components

1. Gi alpha

2. Adenylate cyclase

3. cAMP

4. PKA

Gi pathway sequence of activation

Ligand binds receptor → Giα-GTP inhibits adenylate cyclase → decreases cAMP → reduces PKA activity

Gi pathway final cellular response

Decreased phosphorylation of proteins

Gq pathway components

1. Gq alpha

2. Phospholipase C-beta

3. PIP2

4. DAG

5. IP3

6. Ca2+

7. PKC

Gq pathway sequence of activation

 Ligand binds receptor → Gqα-GTP activates phospholipase C-β → PIP2 is cleaved to DAG and IP3 → IP3 releases Ca2+ → activates PKC and Ca2+-dependent kinases.

Gq pathway final cellular response

Activation of PKC, calcium/calmodulin kinases, and initiation of eicosanoid synthesis

Adaptor proteins (2)

1. AKAP79

2. AKAP250

Adaptor protein function

localize and anchor signaling components to specific sites

AKAP79 function

anchors PKA to adenylate cyclase

AKAP250 function

anchors PKA to phosphodiesterase