A substrate peptide for the FLT3 receptor tyrosine kinase

被引：9

作者：

Boehmer, Frank-D. ^{[1
]}

Uecker, Andrea ^{[1
]}

机构：

[1] Univ Jena, Ctr Mol Biomed, Inst Mol Cell Biol, D-07745 Jena, Germany

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2009年 / 144卷 / 01期

关键词：

FLT3; peptide array; peptide substrate; kinase assay; kinase inhibitor; IN-VIVO; INHIBITORS; LEUKEMIA;

D O I：

10.1111/j.1365-2141.2008.07408.x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

FLT3 (fms-like tyrosine kinase 3) is frequently activated by mutation in acute myeloid leukemia, and is therefore under study as a drug target. Testing and characterization of tyrosine kinase inhibitors is facilitated by the availability of efficient peptide substrates. Searching for FLT3 peptide substrates using phosphorylation experiments on peptide arrays and in solution revealed that the peptide F-T-D-R-L-Q-Q-Y(8)-I-S-T-R-G-L-G is efficiently phosphorylated (apparent Km 10 mu mol/l), with Y8 as the phosphorylated site. This peptide presents a novel tool for identifying and characterizing FLT3 kinase inhibitors.

引用

页码：127 / 130

页数：4

共 14 条

[1]

Cheng Y, 2008, IDRUGS, V11, P46

[2] Signal transduction of oncogenic Flt3 [J].

Choudhary, C ;

Müller-Tidow, C ;

Berdel, WE ;

Serve, H .

INTERNATIONAL JOURNAL OF HEMATOLOGY, 2005, 82 (02) :93-99

[3] Multiple in vivo tyrosine phosphorylation sites in EphB receptors [J].

Kalo, MS ;

Pasquale, EB .

BIOCHEMISTRY, 1999, 38 (43) :14396-14408

[4] Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations [J].

Kancha, Rama Krishna ;

Grundler, Rebekka ;

Peschel, Christian ;

Duyster, Justus .

EXPERIMENTAL HEMATOLOGY, 2007, 35 (10) :1522-1526

[5] FLT3 tyrosine kinase inhibitors [J].

Levis, M ;

Small, D .

INTERNATIONAL JOURNAL OF HEMATOLOGY, 2005, 82 (02) :100-107

[6] Bis(1H-2-indolyl)methanones as a novel class of inhibitors of the platelet-derived growth factor receptor kinase [J].

Mahboobi, S ;

Teller, S ;

Pongratz, H ;

Hufsky, H ;

Sellmer, A ;

Botzki, A ;

Uecker, A ;

Beckers, T ;

Baasner, S ;

Schächtele, C ;

Überall, F ;

Kassack, MU ;

Dove, S ;

Böhmer, FD .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (05) :1002-1018

[7] Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase [J].

Mahboobi, Siavosh ;

Uecker, Andrea ;

Sellmer, Andreas ;

Cenac, Christophe ;

Hoecher, Heymo ;

Pongratz, Herwig ;

Eichhorn, Emerich ;

Hufsky, Harald ;

Truempler, Antje ;

Sicker, Marit ;

Heidel, Florian ;

Fischer, Thomas ;

Stocking, Carol ;

Elz, Sigurd ;

Boehmer, Frank-D. ;

Dove, Stefan .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (11) :3101-3115

[8] SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo [J].

O'Farrell, AM ;

Abrams, TJ ;

Yuen, HA ;

Ngai, TJ ;

Louie, SG ;

Yee, KWH ;

Wong, LM ;

Hong, W ;

Lee, LB ;

Town, A ;

Smolich, BD ;

Manning, WC ;

Murray, LJ ;

Heinrich, MC ;

Cherrington, JM .

BLOOD, 2003, 101 (09) :3597-3605

[9] Flt3 receptor tyrosine kinase as a drug target in leukemia [J].

Schmidt-Arras, D ;

Schwäble, J ;

Böhmer, FD ;

Serve, H .

CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (16) :1867-1883

[10] Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases [J].

Schmidt-Arras, DE ;

Böhmer, A ;

Markova, B ;

Choudhary, C ;

Serve, H ;

Böhmer, FD .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (09) :3690-3703

← 1 2 →