Biomedical Engineering Reference
In-Depth Information
In addition, activated intracellular kinases, such as protein kinases PKA and PKC
also phosphorylate GPCRs and lead to GPCR-G-protein decoupling.
RasGRF Activators
The RasGRF proteins are coupled to G-protein-coupled receptors. Three main
families of guanosine nucleotide-exchange factors (GEF) are associated with Ras
GTPases and link plasmalemmal receptors to Ras protein activation: Son of
sevenless (SOS1-SOS2), Ras guanosine nucleotide releasing factors (RasGRF1-
RasGRF2), and Ras guanosine nucleotide releasing proteins (RasGRP1-RasGRP4;
Vol. 4 - Chap. 9. Guanosine Triphosphatases and Their Regulators). Activators of
the SOS and RasGRP sets link (via GRB2 adaptor and phospholipase-C
-dependent
generation of diacylglycerol, respectively) membrane or cytoplasmic protein Tyr
kinases to Ras GTPases. Calcium influx promotes RasGRF translocation to the
plasma membrane, where it can be phosphorylated (activated).
γ
Gq-Coupled Receptors and Bronchoconstriction
Other Gq-coupled receptors that can cause contraction include A
3
adenosine,
B
2
bradykinin, ET
A
endothelin, H
1
histamine, NK1 and NK
2
neurokinin, and
P2 purinergic receptors [
722
]. Both thrombin and lysophosphatidic acid that operate
via Gq-coupled receptors PARs and LPARs provoke cell proliferation. Endothelin,
histamine, leukotriene-D4, sphingosine 1-phosphate, and thromboxane potentiate
mitogenic effects of receptor protein Tyr kinases via their cognate Gq-coupled
receptors.
High-Affinity Receptors for Leukotriene-B4
For example, high-affinity receptors for leukotriene-B4 (LTb4R), i.e., BLT
1
and
BLT
2
(Vol. 3 - Chap. 7. G-Protein-Coupled Receptors), are expressed on neu-
trophils, eosinophils, and T lymphocytes. They promote leukocyte migration to
the lung and participate in their activation and degranulation. Moreover, they are
produced by human airway smooth myocytes. They are coupled to G
α
i
or G
α
q
subunit. Three forms of the transcribed LTb4R and 2 additional variations in the
5
UTR exist [
721
].
Gs-Coupled Receptors and Bronchodilation
Gs-coupled receptors elicit relaxation of airway smooth myocytes. They comprise
β
2 adrenergic, A
2B
adenosine, prostanoid EP
2
and IP (for prostaglandin-E2 and
prostacyclin, respectively), and vasoactive intestinal peptide (VIP) receptors [
722
].
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