Phospholipases, control proteins

In soils, the activity of extracellular enzymes may be affected as a result of their adsorption to clay particles, which, in turn, influences the microbial life in the soil. Pancreatic lipases and phospholipases control the digestion of alimentary fats in the duodenum. These fats are insoluble in water they are present as emulsified globules. Before the dissolved enzymes can exert their action, they have to adsorb at the surface of the globules. Furthermore, intravascular thrombosis is an interfacial process in which adsorption of proteins at the blood vessel wall enhances the adhesion of blood platelets. 

Phorbol esters are promoters that interact with cellular receptors and activate protein kinase C. Usually protein kinase C is activated by Ca++ and diacylglycerol, both of which result from the hydrolysis of phosphoinositides catalyzed by phospholipase C. Phospholipase C is normally activated by several different growth factors. Thus phorbol esters bypass a tightly regulated step in the control of cell growth. Since protein kinase C phosphorylates various proteins, it is not known how this activity participates in establishing a cancerous line of cells. 

The phospholipases (PLC) isozymes cleave the phosphodiester bond in phos-phatidyl-inositol-4,5-bisphosphate (PIP2) releasing two second messenger molecules inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) as shown before. The /1-isozyme are controlled by the Ga or G y subunits of the heterotrimeric G-proteins coupled to surface receptors. The y-isozymes are substrates for tyrosine kinases, such as growth factors. 

Phosphohpases of type Cy are activated by receptor tyrosine kinases (see Chapter 8), and thus phosphohpase Cy is involved in growth factor controlled signal transduction pathways. The receptor tyrosine kinases (see Chapter 8) phosphorylate the enzyme at specific tyrosine residues and initiate activation of the enzyme. Characteristic for the structure of phospholipase Cy is the occurrence of SH2 and SH3 domains (see Chapter 8). These represent protein modules that serve to attach further partner proteins. 

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... 

Figure 30-19 Major signaling pathways from metabotropic and ionotropic receptors in neurons. Various G proteins control the signaling from mutabo-tropic receptors using phosphatidylinisitol-specific phospholipase C (PI-PLC) and adenylate cyclase or acting directly on K+ ion channels. Adapted from Fig. 5.1 of Nicholls Proteins, Transmitters, and Synapses.149...

Thus, the possibility exists that Ca2+ channels are under dual control by stimulatory and inhibitory G proteins, as well as dual control by protein kinases. However, other explanations may apply. There may be more than one type of ACTH receptors on glomerulosa cells, one activating Gs, the other affecting Ca2+ channels activity by means independent of a G protein, such as activation of phospholipase A2 activity and/or formation of cGMP. Future research in this area should clarify this question. 

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