Mutations of the ras gene product p21 that abolish guanine nucleotide binding.

Clanton, David J.; Hattori, Satoshi; Shih, Thomas Y.

doi:10.1073/pnas.83.14.5076

Cited by 81 publications

(73 citation statements)

References 31 publications

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“…When Asp of Asn-Lys-X-Asp is replaced by Asn as AsnLys-X-Asn in the ras mutant protein, the affinity for GTP is lowered by a factor of 100 [33]. Addi- tionally, in the same protein, a Lys or Tyr replacement of the Asp in Asn-Lys-X-Asp abolishes GTP-binding activity [34]. We did not observe binding of the ATP to S-antigen (not shown), which is consistent with other results [12-141.…”

Section: Resultsmentioning

confidence: 99%

The sequence of human retinal S‐antigen reveals similarities with α‐transducin

Yamaki¹,

Tsuda²,

Shinohara³

1988

FEBS Letters

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The complete amino acid sequence of human retinal S-antigen (48 kDa protein), a retinal protein involved in the visual process has been determined by cDNA sequencing. The largest cDNA was 1590 base pairs (bp) and it contained an entire coding sequence. The similarity of nucleotide sequence between the human and bovine is approximately 80%. The predicted amino acid sequence indicates that human S-antigen has 405 residues and its molecular mass is 45050 Da. The amino acid sequence homology between human and bovine is 81%. There is no overall sequence similarity between S-antigen and other proteins listed in the National Biomedical Research Foundation (NBRF) protein data base. However, local regions of sequence homology with a-transducin (Ta) are apparent including the putative rhodopsin binding and phosphoryl binding sites. In addition, human S-antigen has sequences identical to bovine uveitopathogenic sites, indicating that some types of human uveitis may in part be related to the animal model of experimental autoimmune uveitis (EAU).

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Section: Resultsmentioning

confidence: 99%

The sequence of human retinal S‐antigen reveals similarities with α‐transducin

Yamaki¹,

Tsuda²,

Shinohara³

1988

FEBS Letters

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“…It is known that single amino-acid substitutions within Ras residues 116-119, a region that interacts with the guanine ring, result in a constitutive activation as a result of reduced nucleotide affinity, resulting in GEF-independent nucleotide exchange (Clanton et al, 1986;Walter et al, 1986). It is noteworthy that Rhes maintains the consensus sequence N-K-X-D (NKND in Rhes) within this region.…”

Section: Discussionmentioning

confidence: 99%

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors

et al. 2004

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The Ras homolog enriched in striatum, Rhes, is the product of a thyroid hormone-regulated gene during brain development. Rhes and the dexamethasone-induced Dexras1 define a novel distinct subfamily of proteins within the Ras family, characterized by an extended variable domain in the carboxyl terminal region. We have carried this study because there is a complete lack of knowledge on Rhes signaling. We show that in PC12 cells, Rhes is targeted to the plasma membrane by farnesylation. We demonstrate that about 30% of the native Rhes protein is bound to GTP and this proportion is unaltered by typical Ras family nucleotide exchange factors. However, Rhes is not transforming in murine fibroblasts. We have also examined the role of Rhes in cell signaling. Rhes does not stimulate the ERK pathway. By contrast, it binds to and activates PI3K. On the other hand, we demonstrate that Rhes impairs the activation of the cAMP/PKA pathway by thyroid-stimulating hormone, and by an activated b2 adrenergic receptor by a mechanism that suggests uncoupling of the receptor to its cognate heterotrimeric complex. Overall, our results provide the initial insights into the role in signal transduction of this novel Ras family member.

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“…This region contains the segment of the guanine nucleotide binding pocket including amino acid 117 that interacts with the guanine ring (Figure 7). Single amino-acid substitutions in these positions (116-119) generated by site-directed mutagenesis result in a reduction in binding affinity for GTP (Clanton et al, 1986;Walter et al, 1986). It has been suggested that Ras (D119N) behaves as an activated mutant because of the strongly reduced nucleotide affinity enabling the mutant to bind GTP in a GEF-independent manner (Cool et al, 1999).…”

Section: Discussionmentioning

confidence: 99%