Signal transduction: Thumbs up for inactivation

  title={Signal transduction: Thumbs up for inactivation},
  author={Holger Rehmann and J. L. Bos},
Cellular signalling pathways depend on the proper activation and inactivation of mediators. New structural information reveals an unusual mechanism by which one such mediator, Rap1, is switched off. 
Mechanistic studies on the regulation of Ran-function by post-translational lysine-acetylation
The comprehensive in vitro characterization revealed that acetylation of single lysines impacts on RCC1-interaction and -catalysis, Ran-localization and import-complex formation, and a strong regulatory potential of Ran-acetylation depending on the cellular context is suggested. Expand
Dimerisation‐dependent GTPase reaction of MnmE: how potassium acts as GTPase‐activating element
MnmE, a Guanine nucleotide‐binding protein conserved between bacteria and man, is involved in the modification of tRNAs. Here we provide biochemical and X‐ray structural evidence for a newExpand
Leukocyte adhesion deficiency III: a group of integrin activation defects in hematopoietic lineage cells
The clinical manifestations and molecular basis of this syndrome and related cases will be reviewed, and it seems logical to assume that in all reported cases, a key component of inside-out signaling to integrins activation is involved. Expand
Improving Prospects for Targeting RAS.
This work discusses the various approaches under investigation to target mutant RAS proteins, and the recent development of direct RAS inhibitors specific to KRAS G12C mutations represents a landmark discovery that promises to change the perception about RAS's druggability. Expand
Biochemische Charakterisierung neuartiger GTPase aktivierender Proteine der Rho-Familie aus Pflanzen
ROPs \(\textit {rho of plants}\) sind pflanzenspezifische GTP-bindende Proteine, deren langsame intrinsische GTP-Hydrolyse durch GTPase aktivierende Proteine (GAP) katalysiert wird, wodurch eineExpand
The role of p19 C-H-Ras protein in metastasis and proliferative pathways
En esta tesis doctoral hemos encontrado evidencias que sugieren that la proteina p19 c-H-Ras promueve a un estado anticancerigeno en la celula, mientras that the proteinas H-RAs induce the aparicion of algunos aspectos del proceso maligno. Expand


Rap1 signalling: adhering to new models
Ras-like GTPases are ubiquitously expressed, evolutionarily conserved molecular switches that couple extracellular signals to various cellular responses, ranging from modulation of growth and differentiation to secretion, integrin-mediated cell adhesion and morphogenesis. Expand
RanGAP mediates GTP hydrolysis without an arginine finger
The structure and biochemical experiments show that RanGAP does not act through an arginine finger, that the basic machinery for fast GTP hydrolysis is provided exclusively by Ran and that correct positioning of the catalytic glutamine is essential for catalysis. Expand
The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants.
The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Expand
The GTPase-activating protein Rap1GAP uses a catalytic asparagine
It is demonstrated that Rap1GAP provides a catalytic asparagine to stimulate GTP hydrolysis and implications for the disease tuberous sclerosis are discussed. Expand
Structure at 1.65 Å of RhoA and its GTPase-activating protein in complex with a transition-state analogue
The crystal structure of RhoA and rhoGAP complexed with the transition-state analogue GDP is reported and it is proposed that this residue acts to stabilize the transition state of the GTPase reaction. Expand
Amino acid 61 is a determinant of sensitivity of rap proteins to the ras GTPase activating protein.
It is shown that ras-GAP can interact with rap and that the sensitivity to ras, the GTPase activating protein, is determined in part by the amino acid at codon 61, and mutated thr61 of p21rap1A to glutamine to accelerate the rate of hydrolysis of GTP. Expand
Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.
AlF4- complexes formed by the G protein Gi alpha 1 demonstrate specific roles in transition-state stabilization for two highly conserved residues, suggesting a mechanism that may promote release of the beta gamma subunit complex when the alpha subunit is activated by GTP. Expand
Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
It is shown that the small GTPase Rheb (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro. Expand
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis.
The region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Expand
ras oncogenes in human cancer: a review.
  • J. Bos
  • Biology, Medicine
  • Cancer research
  • 1989
It appeared that ras gene mutations can be found in a variety of tumor types, although the incidence varies greatly and some evidence that environmental agents may be involved in the induction of the mutations. Expand