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- Title
Angiotensin II, the AT[sub 2] receptor, and nuclear factor-κB activation.
- Authors
Luft, Friedrich C.
- Abstract
Angiotensin (Ang) II induces many proinflammatory and growth-inducing effects. The nuclear transcription factor-κB (NF-κB) is important to both. Ang II signals primarily via two receptors, termed AT[sub 1] and AT[sub 2] Most of the Ang II-related actions familiar to us are mediated by the AT[sub 1] receptor and the intermediate steps have been fairly well explained. Both Ang II receptors belong to the seven transmembrane-domain receptor family; but oddly enough, exhibit only 34% homology. In fact, the AT[sub 2] receptor has the same homology to the somatostatin receptor subtypes as to the AT[sub 1] receptor. The two Ang II receptors should therefore have substantially different functions. AT[sub 2] receptor signaling has generated much interest, but nevertheless remains mysterious [1, 2]. Apparently, Ca[sup 2+] and cyclic 3',5 'adenosine monophosphate (cAMP) are not involved and the receptor is not internalized. The receptor appears to activate phosphorylases and attenuates phosphorylation steps important to growth signaling. Mitogen-activated protein (MAP) kinase activation is inhibited presumably by dephosphorylation via the MAP kinase phosphatase, MKP-1 [1]. The activation or inactivation of extracellular signal-regulated protein kinase (ERKs) via AT[sub 2] is controversial and appears to be either condition-, cell-line-, or costimulation-dependent [1]. Since AT[sub 2] receptor expression is most prominent during embryonic development, its role in the adult is even less clear. However, evidence has been submitted indicating that the AT[sub 2] receptor stimulates a vasodilator signaling cascade that includes bradykinin, nitric oxide, and cyclic guanosine 3,'5' monophosphate (cGMP) in adult animals. These findings suggest that the AT[sub 2] receptor may be relevant to blood pressure regulation. An incomplete comparison between the seven transmembrane-spanning domains between AT[sub 1] and AT[sub 2] follows [1, 2].
- Subjects
ANGIOTENSINS; NF-kappa B
- Publication
Kidney International, 2002, Vol 61, Issue 6, p2272
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00388.x