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Effector enzymes coupled to GTP-binding proteins (Phospholipase C (Beta,…
Effector enzymes coupled to GTP-binding
proteins
Adenylyl Cyclase
Phosphorylation of
PKA: 2 R(egulatory) sites, 2 C(atayltic) sites
PKA activation, cAMP -> AMP
Galpha (ATP -> cAMP)
AC Structure
40-60% homology
Mn and Mg2+ stabilise ATP hydrolysis
C1 and C2 form active site together
Crosstalk
Pseudosymmetrical
9 Isoforms, 1-8 activated by Galpha and inhibited by P-site inhibitors
AC Activators and Inhibitors
PKC phosphorylation enhances II, V, and VII
Aluminium fluoride, Forskolin
cAMP -> PKA -> feedback inhibition of V and VI
Cholera toxin and pertussis toxin: ADP ribosylation
PLC: indirectly activates AC by increasing Ca
GLycogen phosphorylase cascade
Phospholipase C
Beta, gamma, delta isoforms
PH domain, EF-hand motifs, C2 domain
PIP2 -> DAG + IP3
B-isoform: activated by alpha subunit of Gq, By subunit of Gi and Go
cleaves polar group from memebrane glycerophospholipids
y-isoform activated by tyrosine kinase interaction
IP3 and DAG recycled by specific pathways into PIP2
IP3
Release of Ca from ER or SR
DAG
Activates TRP channels
Increases Ca sensitivity via PKC phosphorylation of proteins