Protein category | Function |
---|---|
Adenylate cylcase | Transmembrane protein regulated by G protein; catalyzes formation of the second messenger cyclic adenosine monophosphate (cAMP) from ATP. |
ATP-sensitive inward rectifier K + channels | Regulated by G proteins and GRKs. Activation leads to hyperpolarization and reduction of membrane excitability. |
G protein (Gα,β,γ) | Heterotrimeric protein composed of α,β, and γ subunits; activated by GPCR to bind to and activate/deactivate various effectors (e.g. second messengers); amplifies receptor signal. The α-subunit is divided into several sub-types that perform different functions by activating various effector proteins: α(q) activates PLC, α(s) activates the cAMP-dependent pathway via activation of AC, α(i) inhibits AC and thus cAMP production and α(12/13) activates Rho GTPases. |
G protein-coupled receptor (GPCR) | Cell surface receptor; binds agonist/ligand, catalyzing exchange of GDP for GTP on G protein; dissociates and activates G protein subunits. |
GPCR kinase (GRK) | Regulates GPCR activity via phosphorylation; desensitizes the receptor signal. |
Phosphodiesterase | Degrades the phosphodiester bond in the second messengers cAMP and cGMP; terminates receptor signal. |
Phosphoinositide-3 kinase (PI3K) | Recruited to the cell membrane following GPCR activation; binds G protein and initiates assembly of signaling complexes and priming of protein kinase cascades; hyperactivation of this pathway has been associated with cancer and diabetes. |
Phospholipase C | Catalyzes hydrolysis of phospholipids to generate the second messengers inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG); amplifies signal by stimulating Ca2+ release and protein kinase activation. |
Protein kinase C | Regulates signal transduction; activated by G proteins or increases in cytosolic Ca2+; phosphorylates a wide variety of proteins including small GTPases and MAPKs |
Raf | Member of the serine/threonine-specific protein kinases that functions downstream of the Ras subfamily. Raf activates the MAPK/ERK pathway. |
Rap1GAP | Encodes a GTPase-activating protein that down-regulates the activity of the RAP1 protein. RAP1 is a Ras subfamily protein. |
RasGAP | Stimulates the GTPase activity of Ras, thereby inactivating Ras. Ras acts as a molecular switch, functioning within a signal transducing cascade of reactions. |
Regulator of G protein signaling (RGS) | Inactivates G protein, leading to rapid turnoff of GPCR signaling. RGS promotes GTP hydrolysis by the G protein α-subunit. |
RhoGEF | Structural domain of guanine nucleotide exchange factors for Rho-like GTPases that controls Rho signaling by mediating GDP release from Rho and replacing with GTP. |
Rho small GTPases | Family of small signaling G proteins that are homologous to Gα subunit but are monomeric in structure. These proteins interact with and activate effector proteins that mediate downstream signaling. |
SHC transforming proteins | Src homology 2 domain containing protein. Links activated tyrosine receptor kinases to the Ras pathway. |
Tyrosine receptor kinases | Cell surface receptor that link GPCRs to the Ras-MAPK pathway. Activated by the G protein βγ subunit and in turn stimulates the Ras subfamily proteins. |
Voltage dependent Ca2+ channels | Modulates calcium influx into the cell. GPCRs play critical role in negative feedback to inhibit the activity of these channels via direct interaction with the G protein βγ subunit. |