Hormonal Regulation of Phospholipid Metabolism via G-proteins II: PLA2 and Inhibitory Regulation of PLC
Lipid derivatives play a major role as second messengers. A large body of evidence has accumulated on the mechanisms leading to their formation and on their role in cell regulation (reviewed in Dennis et al. 1991). They are formed by the action of different phospholipases (A2, C, D) acting on membrane phospholipids. Of particular physiological relevance has been the elucidation of the hormonal regulation of these enzymes. A large number of receptors for hormones and neurotransmitters are coupled to cellular phospholipases and regulate the cytosolic levels of second messengers such as Ca2+, diacylglycerol, inositol trisphosphate, and arachidonic acid. The activation of phospholipases can be indirectly induced by a receptormediated increase in cytosolic Ca2+, or it can be due to the activation of a heterotrimeric GTP-binding (G) protein directly coupled to the enzyme.
KeywordsArachidonic Acid Adenylyl Cyclase Pertussis Toxin Thyroid Cell PLA2 Activity
Unable to display preview. Download preview PDF.
- Di Girolamo M, D’Arcangelo D, Cacciamani T, Gierschik P, Corda D (1992) K-ras transformation greatly increases the toxin-dependent ADP-ribosylation of GTP binding proteins in thyroid cells. Involvement of an inhibitor of the ADP-ribosylation reaction. J Biol Chem 267:17397–17403.PubMedGoogle Scholar
- Enjalbert A, Sladeczek F, Guillon G, Bertrand P, Shu C, Epelbaum J, Garcia-Sainz A, Jard S, Lombard C, Kordon C, Bockaert J (1986) Angiotensin II and dopamine modulate both cAMP and inositol phosphate productions in anterior pituitary cells. Involvement in prolactin secretion. J Biol Chem 261:4071–4075.PubMedGoogle Scholar
- Enjalbert A, Guillon G, Mouillac B, Audinot V, Rasolonjanahary R, Kordon C, Bockaert J (1990) Dual mechanisms of inhibition by dopamine of basal and thyrotropin-releasing hormone-stimulated inositol phosphate production in anterior pituitary cells. Evidence for an inhibition not mediated by voltage-dependent Ca2+ channels. J Biol Chem 265:18816–18822.PubMedGoogle Scholar
- Huang NN, Wang DJ, Gonzalez F, Heppel LA (1991) Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells. II. A pathway involving arachidonic acid release, prostaglandin synthesis, and cyclic AMP accumulation. J Cell Physiol 146:483–494.PubMedCrossRefGoogle Scholar
- Jelsema CL, Burch RM, Jaken S, Ma AD, Axelrod J (1989) Modulation of phospholipase A2 activity in rod outer segments of bovine retina by G protein subunits, guanine nucleotides, protein kinases, and calpactin. In Redburn DA, Pasantes-Morales H (eds) Extracellular and intracellular second messengers in the vertebrate retina, vol 49, Neurology and neurobiology, Alan R. Liss New York, pp 25–46.Google Scholar
- Narasimhan V, Holowka D, Baird B (1990) A guanine nucleotide-binding protein participates in IgE receptor-mediated activation of endogenous and reconstituted phospholipase A2 in a permeabilized cell system. J Biol Chem 264:1459–1464.Google Scholar