Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 395

Activated Gs stimulates membrane-bound adenylate cyclase AC5 and AC6
isoforms. Activated adenylate cyclases create second messenger cAMP from
ATP to activate protein kinase-A. This enzyme can phosphorylate some Gq-
coupled receptors, phospholipase-C, as well as IP 3 Rs to prevent phosphoinositide
generation and calcium influx. It also phosphorylates myosin light chain kinase,
thereby reducing its affinity to calcium-calmodulin and activity. It phosphorylates
calcium-activated potassium channel to cause K + efflux and hyperpolarization.
It phosphorylates the transcription factor cAMP-responsive element-binding protein
(CREB) to control the synthesis of numerous immunomodulatory proteins.

VIP Receptor

Vasoactive intestinal peptide (VIP), a relaxant neuropeptide, impedes translocation
of cRaf to the plasma membrane induced by ceramide as well as that of PKC [ 723 ].

The Ras-mediated signaling links plasmalemmal receptors to mitogen-activated
protein kinase modules that phosphorylate (activate) several target proteins such
as 27-kDa heat shock protein (HSP27). In smooth myocytes, HSP27 colocalizes
with actin filaments and proteins of the contractile cytoskeleton, such as myosin,
tropomyosin, and caldesmon to modulate the interaction between these proteins.
Phosphorylation of HSP27 promotes actin polymerization and stress fiber for-
mation. In airway smooth myocytes, phosphorylated HSP27 stabilizes the actin
cytoskeleton [ 724 ].

α

Gi-Coupled Receptors

A third group of GPCRs preferentially couples to members of the G α i family

(Gi1-Gi3). Activated Gi hampers the activity of adenylate cyclases. On the other
hand, Gi and/or G

subunits stimulate Rho guanine nucleotide-exchange factors,
hence Rho GTPases for actin polymerization. Dimer G

βγ

inhibits AC1, but can
enhance the activity of certain adenylate cyclase isoforms, such as AC2, AC4, and
AC7, as well as sensitization of adenylate cyclases to stimuli [ 722 ]. In addition,
G

βγ

βγ can activate phospholipase-C β .

G12/13-Coupled Receptors

A forth set of G-protein-coupled receptors associate with members of the G12/13
subclass. Their effectors encompass members of a family of guanine nucleotide-
exchange factors for small Rho GTPases. G12/13-coupled receptors may include
LPA, S1P, peptidase-activated (PAR), and prostanoid TP (for thromboxane-A2)
receptors [ 722 ].