Browning mutant proteins

M. S. Brown. cDNA cloning of MEV, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function. J. Biol. Chem. 1992, 267, 23113-23121. 

PasineUi P, Belford ME, Lennon N, Bacskai BJ, Hyman BT, Trotti D, Brown RH Jr. (2004) Amyotrophic lateral sclerosis-assodated SODl mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43 19-30... 

Bennett, D. C., Huszar, D., Laipis, P. J Jaenisch, R., and Jackson, I. J. (1990). Phenotypic rescue of mutant brown melanocytes by a retrovirus carrying a wild-type tyrosinase-related protein gene. Development 110 471-475. 

Hiroi, N., Brown, J.R., Haile, C.N. et al. FosB mutant mice loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine s psychomotor and rewarding effects. Proc. Natl. Acad. Sci. U.S.A. 94 10397, 1997. 

Ratjen E, Doring G. Cystic fibrosis. Lancet 2003 361 681-689. Brown CR, Hong-Brown LQ, Biwersi J, Verkman AS, Welch WJ. Chemical chaperones correct the mutant phenotype of the delta E508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones. 1996 1 117-125. 

Golgi apparatus, the nucleus, and the plasma membrane (Donaldson and Klausner, 1994). The identification of ARFs as activators of an isoform of phospholipase D (Brown etal., 1993 Cockcroft eta/., 1994 /Vlassenburg ef a/., 1994 Hammond et a/., 1995), which appears to be present (at least in part) in the Golgi apparatus (Ktistakis etal., 1995), has helped to define further the function of ARF in cells. Investigations into the role of ARFs in these processes have employed recombinant wild-type and mutant ARF constructs. Thus, the assays discussed here have become commonly used to measure native ARFs, and to assess the integrity of recombinant proteins and the effects of mutations on their activity. 

Goldstein, J.L., Rawson, R.B., Brown, M.S. 2002. Mutant mammalian cells as tools to delineate the sterol regulatory element-binding protein pathway for feedback regulation of lipid synthesis. Arch. Biochem. Biophys. 397 139-148. 

Sacks WR, Schaffer PA (1987) Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICPO exhibit impaired growth in cell culture. J Virol 61 829-839 Spector FC, Kern ER, Palmer J, Kaiwar R, Cha TA, Brown P, Spaete RR (1998) Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex virus type 2 vaccine in guinea pigs. J Infect Dis 177 1143-1154... 

Lipids have been found to be critical regulators of Arf GAP activity. Both the substrate Arfl GTP and the catalytic Arf GAPs associate with lipids. We have identified point mutants of Arfl that do not require the presence of lipids to bind GTP (Yoon et al, 2004) however, even with soluble Arfl mutants, each Arf GAP requires lipid for optimal activity (Bigay et al, 2003 Brown et al, 1998 Jackson et al, 2000 Kam et al, 2000 Nie et al, 2002 Randazzo and Kahn, 1994). Furthermore, the lipid requirements are unique to particular Arf GAPs, with proteins being sensitive to both composition and form of the hpids. 

Peer WA, Brown DE, Tague BW, etal. (2001) Flavonoid accumulation patterns of transparent testa mutants of Arabidopsis. Plant Physiol 126 536-548 Peer WA, Bandyopadhyay A, Blakeslee JJ, et al. (2004) Variation in expression and protein localization of the PIN family of auxin efflux facilitator proteins in flavonoid mutants with altered auxin transport in Arabidopsis thaliana. Plant Cell 16 1898-1911... 

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