Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText.
Kick-your-searchterm to multiple Engines kick-your-query now !>
A dictionary by aggregated review articles of nephrology, medicine and the life sciences
Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

suck abstract from ncbi


10.1093/hmg/dds426

http://scihub22266oqcxt.onion/10.1093/hmg/dds426
suck pdf from google scholar
23059812!ä!23059812

suck abstract from ncbi


Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534

Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
pmid23059812      Hum+Mol+Genet 2013 ; 22 (2): 262-70
Nephropedia Template TP

gab.com Text

Twit Text FOAVip

Twit Text #

English Wikipedia


  • Diverging gain-of-function mechanisms of two novel KRAS mutations associated with Noonan and cardio-facio-cutaneous syndromes #MMPMID23059812
  • Cirstea IC; Gremer L; Dvorsky R; Zhang SC; Piekorz RP; Zenker M; Ahmadian MR
  • Hum Mol Genet 2013[Jan]; 22 (2): 262-70 PMID23059812show ga
  • Activating somatic and germline mutations of closely related RAS genes (H, K, N) have been found in various types of cancer and in patients with developmental disorders, respectively. The involvement of the RAS signalling pathways in developmental disorders has recently emerged as one of the most important drivers in RAS research. In the present study, we investigated the biochemical and cell biological properties of two novel missense KRAS mutations (Y71H and K147E). Both mutations affect residues that are highly conserved within the RAS family. KRAS(Y71H) showed no clear differences to KRAS(wt), except for an increased binding affinity for its major effector, the RAF1 kinase. Consistent with this finding, even though we detected similar levels of active KRAS(Y71H) when compared with wild-type protein, we observed an increased activation of MEK1/2, irrespective of the stimulation conditions. In contrast, KRAS(K147E) exhibited a tremendous increase in nucleotide dissociation generating a self-activating RAS protein that can act independently of upstream signals. As a consequence, levels of active KRAS(K147E) were strongly increased regardless of serum stimulation and similar to the oncogenic KRAS(G12V). In spite of this, KRAS(K147E) downstream signalling did not reach the level triggered by oncogenic KRAS(G12V), especially because KRAS(K147E) was downregulated by RASGAP and moreover exhibited a 2-fold lower affinity for RAF kinase. Here, our findings clearly emphasize that individual RAS mutations, despite being associated with comparable phenotypes of developmental disorders in patients, can cause remarkably diverse biochemical effects with a common outcome, namely a rather moderate gain-of-function.
  • |*Mutation[MESH]
  • |Cell Line[MESH]
  • |Ectodermal Dysplasia/*genetics/*metabolism[MESH]
  • |Facies[MESH]
  • |Failure to Thrive/*genetics/*metabolism[MESH]
  • |Heart Defects, Congenital/*genetics/*metabolism[MESH]
  • |Humans[MESH]
  • |Noonan Syndrome/*genetics/*metabolism[MESH]
  • |Protein Binding[MESH]
  • |Protein Conformation[MESH]
  • |Protein Stability[MESH]
  • |Signal Transduction[MESH]


  • DeepDyve
  • Pubget Overpricing
  • suck abstract from ncbi

    Linkout box