E-viri
Recenzirano
Odprti dostop
-
Hu, Jiancheng; Stites, Edward C.; Yu, Haiyang; Germino, Elizabeth A.; Meharena, Hiruy S.; Stork, Philip J.S.; Kornev, Alexandr P.; Taylor, Susan S.; Shaw, Andrey S.
Cell, 08/2013, Letnik: 154, Številka: 5Journal Article
Although RAF kinases are critical for controlling cell growth, their mechanism of activation is incompletely understood. Recently, dimerization was shown to be important for activation. Here we show that the dimer is functionally asymmetric with one kinase functioning as an activator to stimulate activity of the partner, receiver kinase. The activator kinase did not require kinase activity but did require N-terminal phosphorylation that functioned allosterically to induce cis-autophosphorylation of the receiver kinase. Based on modeling of the hydrophobic spine assembly, we also engineered a constitutively active mutant that was independent of Ras, dimerization, and activation-loop phosphorylation. As N-terminal phosphorylation of BRAF is constitutive, BRAF initially functions to activate CRAF. N-terminal phosphorylation of CRAF was dependent on MEK, suggesting a feedback mechanism and explaining a key difference between BRAF and CRAF. Our work illuminates distinct steps in RAF activation that function to assemble the active conformation of the RAF kinase. Display omitted •RAF dimers are asymmetric with one component allosterically activating the other•N-terminal phosphorylation but not kinase activity is required on the activator•Dimerization induces cis-autophosphorylation of the RAF activation loop•Mutations that stabilize the active conformation do not require dimerization RAF kinase dimerization is important for its activation. Dimerization allosterically induces the active kinase conformation through the asymmetric phosphorylation of the activation loop on one molecule, which activates the second molecule by inducing its cis-autophosphorylation.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.