H-Ras

Figure 9-2. Based on ihe conjugated backbone of a /H/ra-phenylcne the most common principle structures of conjugated molecules am described (a) the pure backbone (b) a backbone with attached side-groups R and R (e) a ladder type-eonjugaled backbone (d) and (c) represent different types of copolymers. where (d) represents a side cliain-gnill copolymer and (c) a single eliain-bloek copolymer.

N-ras, H-ras, K-ras Signal transduction pathway Inhibition of cell proliferation and colony formation change in morphology, enhanced melanin synthesis decrease of in vivo tumorigenicity... 

Scheme 104. Synthesis of the protoemetine derivative 500. Reagents a, Li, liq NH3, /-BuOH b, NCS, CH2C12 c, H2/Pd-C, MeOH d, pyrrolidine, benzene e, (TsSCH2)2CH2 f, KOH, /-BuOH, THF g, CH2N2 h, Ra-Ni, MeOH.

Desulfurization of organic compounds over Ra-Ni is a well-known procedure.364-369 Ra-Ni exists in different forms (W1 to W8), differing in the preparation procedure and sometimes symbolized as Ni(H). Ra-Ni is sometimes called a catalyst however, it is used usually in large excess and the reaction is stoichiometric. Ra-Ni can desulfurize every C—S bond containing compound but it can also hydrogenate a lot of other functional groups. Unwanted side reactions are sometimes suppressed by using deactivated Ra-Ni. 

Ratnam, S. and Kent, C. (1995) Early increase in choline kinase-activity upon induction of the H-Ras oncogene in mouse fibroblast cell-lines. Archives of Biochemistry and Biophysics 323, 313—322. 

Finally, GTP is bound by many proteins, and diazirine-bearing thiol-cleavable GTP analogs (e.g., 23) have been proposed as probes to detect such proteins. By this method, H-Ras was successfully labeled in a nuclear extract of cultured human cells [70]. 

The membrane-associated small G proteins H-Ras and K-Ras have been studied with respect to their association with cytoplasmic leaflets. These two proteins have nearly identical structures and functions but different membrane anchors, membrane distributions and effector responses. Application of the FRAP method to fluorescent constructs of H-Ras and K-Ras revealed that only H-Ras in its guanosine 5 diphosphate (GDP)-bound form associates with cholesterol-dependent rafts [26]. 

In addition to fluorescence methods, another study [27] developed a method to permit electron microscopic localization of Ras anchor domains on cytoplasmic membrane surfaces by immunogold labeling. The particle neighbor distances can be analyzed to obtain information about possible domain structure. Expressing H-Ras and K-Ras in baby hamster kidney cells, a nonrandom particle distribution was obtained from which the estimated mean raft size was 7.5-22 nm and about 35% of the membrane area consists of rafts. The same technique applied to cells that had been incubated with [3-cydodextrin to reduce cholesterol produced completely random distributions of H-Ras. This cholesterol dependence suggests some type of coupling of rafts across the inner and outer membrane leaflets. 

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