|Budget Amount *help
¥82,290,000 (Direct Cost : ¥63,300,000、Indirect Cost : ¥18,990,000)
Fiscal Year 2014 : ¥19,370,000 (Direct Cost : ¥14,900,000、Indirect Cost : ¥4,470,000)
Fiscal Year 2013 : ¥20,280,000 (Direct Cost : ¥15,600,000、Indirect Cost : ¥4,680,000)
Fiscal Year 2012 : ¥21,320,000 (Direct Cost : ¥16,400,000、Indirect Cost : ¥4,920,000)
Fiscal Year 2011 : ¥10,530,000 (Direct Cost : ¥8,100,000、Indirect Cost : ¥2,430,000)
Fiscal Year 2010 : ¥10,790,000 (Direct Cost : ¥8,300,000、Indirect Cost : ¥2,490,000)
|Outline of Final Research Achievements
CBLis a RING-type E3 ubiquitin ligase that functions as a negative regulator of T-cell activation and growth factor receptor and nonreceptor-type tyrosine kinase signaling. NMR and small angle X-ray scattering analyses revealed that the unphosphorylated N-terminal region of CBL forms a compact structure by an intramolecular interaction, which masks interaction surface of the RING domain with an E2 ubiquitin-conjugating enzyme. Phosphorylation of Y371 disrupts the interdomain interaction to expose the E2 binding surface of the RING domain for efficient ubiquitination.
Ordered phosphorylation is required for receptor tyrosine kinase (RTK) activation; a process mediated by transient dimer formation of the kinase domains. This process is triggered by the tyrosine phosphorylation in the activation-loop. Here, we report structural and biochemical analyses of the tyrosine kinase domain interaction of FGFR required for the initial phosphorylation step.