Helices phospholipases

Two pathways from the activated receptor are shown. At the left is activation of phospholipase Cy and formation, at a membrane-bound site, of inositol trisphosphate and diacylglycerol (DAG). The main pathway, in the center, activates Ras with the aid of the G protein Sos. Activated Ras, in turn, activates Raf and successive components of the MAPK cascade. At the right a seven-helix receptor activates both phospholipase C(3 and Ras via interaction with a (3y subunit. (B) A generalized scheme for the MAP kinase pathway. See Seger and Krebs.380... 

Angiotensin II has a variety of effects. By constricting blood vessels it raises blood pressure, and by stimulating thirst centers in the brain it increases blood volume. Both angiotensins II and III also act on the adrenal gland to promote the synthesis and release of aldosterone. Most of the effects of angiotension II are mediated by 359-residue seven-helix G-protein linked receptors which activate phospholipase C.p q qr Like other steroid hormones aldosterone acts,via mineralocorticoid receptors, to control transcription of a certain set of proteins. The end effect is to increase the transport of Na+ across the renal tubules and back into the blood. Thus, aldosterone acts to decrease the loss of Na+ from the body. It promotes retention of water and raises... 

Many other receptors are 7-helix transmembrane proteins, which activate guanine nucleotide G proteins (Chapter 11, Section D, 3). The G proteins couple some receptors directly to Ca2+ channels they couple other receptors to adenylate cyclase and cyclic AMP-activated channels and yet others via phospholipase C to K+ channels and indirectly to Ca2+ channels (Fig. 30-19). All of these G protein coupled receptors are referred to as metabotropic receptors. A single synapse often contains both ionotropic receptors and metabotropic receptors. The ionotropic receptors induce a rapid (< 1 ms) response, while the metabotropic receptors act more slowly. However, in most cases the final effect is the release of calcium ions into the cytoplasm... 

Both adrenaline and noradrenaline stimulate smooth muscles throughout the body and have a hypertensive effect. Their postsynaptic receptors are 7-helix transmembrane proteins (Fig. 11-6). A comparison of the effects of various analogs led to the classification of these receptors into classes a, a2, P, and P2, which are discussed briefly on pp. 553-555. The a receptors, which are structurally closely related to rhodopsin,753/754 are coupled via Gq /11 proteins to a phosphoinositide-activated phospholipase C (Figs. 11-9, 30-19).755 They usually provoke an excitatory response. However, in intestinal smooth muscles they are inhibitory. Adrenaline is usually more active at a receptors than is noradrenaline. A specific antagonist... 

NMR confirms the presence of the amino-terminal helix of group II phospholipase A2 in... 

Fig. 5. The amino terminus of class I/II secretory phospholipases A. Schematic stereoview of the web of hydrogen bonds that stabilizes the amino terminus of class I/II enzymes (class II Crotalus atrox) (Brunie et al., 1985 Scott et al., 1992, copyrighted by the Journal of Biological Chemistry). Modification of the amino terminus (e.g., transamination) structurally disorders the adjacent helix and peptide. A Gin is almost invariant at sequence position 4. Replacement of Gln-4 with an Asn, as in the human nonpancreatic enzyme, permits small (<1 A) movements of the amino-terminal helix, which can narrow the hydrophobic channel (Scott e/a/., 1991).

P. Glynn and co-workers showed that NTE is anchored to the cytoplasmic face of the endoplasmic reticulum (ER) via its transmembrane helix (TM), its R-and C-domains also interact with the cytoplasmic face of the ER [39], It has been found that NTE possesses phospholipase [44] and lisophospholipase activity [46] in addition to its ability to hydrolyze carboxy ester substrates [3,12,41], The last published work from this lab demonstrated that NTE and its homologues deacylate phosphatidylcholine, the major membrane lipid in eukaryotic cells, to glycerophosphocholine and by this means play a central role in membrane lipid homeostasis [47],... 

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