Low-molecular-weight G-proteins

In addition to the large, heterotrimeric G-proteins that have been shown to play a role in signal transduction, a superfamily of low-molecular-weight (LMW) GTP-binding proteins, which are structurally related to ras, has been shown also to play important roles in the regulation of cell function. These proteins were initially identified by molecular cloning techniques and 

The ras superfamily of proteins in mammalian cells is divided into three subgroups, depending upon the degree of homology between the proteins (Table 6.1)  

Ki-ras and N-ras. Expression of rapl A (also known as Krev-1) causes the reversion of cells that have been transformed by Ki-ras, and so the function of p21 raplA may counteract the action of ras proteins. 

---

Eklund, E. A., Marshall, M Gibbs, J. B Crean, C. D Gabig, T. G. (1991). Resolution of a low molecular weight G protein in neutrophil cytosol required for NADPH oxidase activation and reconstitution by recombinant Krev-1 protein. J. Biol. Chem. 266, 13964-70. 

Figure 6.4. Mode of action of low-molecular-weight G-proteins. The raslike proteins normally bind GDP, but this may be exchanged for GTP via a process that may be assisted by guanine nucleotide exchange protein (GNEP). The GTP-bound ras protein may then interact with and activate its target protein (X). The activity of GTPase activating protein (GAP) may then assist to hydrolyse GTP to GDP, to inhibit ras activity.

Receptors for ADP, epinephrine, thromboxane, thrombin and PAF have been well characterized (27, 31, reviewed in other chapters). Membrane spanning receptors of epinephrine, t mbin and thromboxane are coupled to the ubiquitous GTP-hinding proteins. Platelets contain monomeric, low molecular weight G proteins as well as heterotrimeric membrane associated G roteins. GTP binding to e a-subunit of G-proteins fiicilitates die interaction with effector enzymes, resulting in the hydrolysis of GTP to GDP, which terminates its stimulatory role (29). 

In addition to the conventional, direct signalling from SIP and LPA receptors via heterotrimeric and low molecular weight G-proteins (see above), signals... 

Two classes of antioxidants are known the low-molecular weight compounds (tocopherols, ascorbate, -carotene, glutathione, uric acid and etc.) and the proteins (albumin, transferrin, caeruloplasmin, ferritin, etc.) including antioxidant enzymes (e.g. superoxide dismutase, catalase, glutathione peroxidase). 

This chapter lists some representative examples of biochemicals and their origins, a brief indication of key techniques used in their purification, and literature references where further details may be found. Simpler low molecular weight compounds, particularly those that may have been prepared by chemical syntheses, e.g. acetic acid, glycine, will be found in Chapter 4. Only a small number of enzymes and proteins are included because of space limitations. The purification of some of the ones that have been included has been described only briefly. The reader is referred to comprehensive texts such as the Methods Enzymol (Academic Press) series which currently runs to more than 344 volumes and The Enzymes (3rd Edn, Academic Press) which runs to 22 volumes for methods of preparation and purification of proteins and enzymes. Leading referenees on proteins will be found in Advances in Protein Chemistry (59 volumes. Academic Press) and on enzymes will be found in Advances in Enzymology (72 volumes, then became Advances in Enzymology and Related Area of Molecular Biology, J Wiley Sons). The Annual Review of Biochemistry (Annual Review Inc. Patio Alto California) also is an excellent source of key references to the up-to-date information on known and new natural compounds, from small molecules, e.g. enzyme cofactors to proteins and nucleic acids. 

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

Chemokines are a superfamily of low-molecular-weight chemotactic cytokines that exert their effects through seven transmembrane domain G protein-coupled receptors. Although some chemokines are constitutively expressed in certain settings, most are induced by proinflammatory mediators, such as IFN-y and TNF-a. Upon binding to the appropriate receptor, chemokines initiate a... 

From these observations, we have noticed the similarity of the simple lattice inclusions to the more sophisticated assemblies of molecules (e.g. cyclodextrins 76 and proteins 78 where the formation of H-bonded loops was first detected and described. Conclusively the motive for the formation of simple inclusion crystals and of more complex associates between high and low molecular weight compounds, such as enzyme-substrate complexes, can be traced back to the same source. 

Iron transport agents may belong to the protein or non-protein class. In the former group are found the animal proteins transferrin (25), lactoferrin (26) and conalbumin (27). The low molecular weight iron carrying compounds from microorganisms, the siderochromes, may occur with or without a bound metal ion. Typically, severe repression of biosynthesis of these substances can be expected to set in at an iron concentration of ca. 2 x 10-5 g atoms/liter (28). Most, but not all, of these substances can be described as phenolates or hydroxamates (4). 

---