A Specific Need for CRKL in p210BCR-ABL–Induced Transformation of Mouse Hematopoietic Progenitors
Open Access
- 14 September 2010
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 70 (18), 7325-7335
- https://doi.org/10.1158/0008-5472.can-10-0607
Abstract
CRKL (CRK-like) is an adapter protein predominantly phosphorylated in cells that express the tyrosine kinase p210BCR-ABL, the fusion product of a (9;22) chromosomal translocation causative for chronic myeloid leukemia. It has been unclear, however, whether CRKL plays a functional role in p210BCR-ABL transformation. Here, we show that CRKL is required for p210BCR-ABL to support interleukin-3–independent growth of myeloid progenitor cells and long-term outgrowth of B-lymphoid cells from fetal liver–derived hematopoietic progenitor cells. Furthermore, a synthetic phosphotyrosyl peptide that binds to the CRKL SH2 domain with high affinity blocks association of endogenous CRKL with the p210BCR-ABL complex and reduces c-MYC levels in K562 human leukemic cells as well as in mouse hematopoietic cells transformed by p210BCR-ABL or the imatinib-resistant mutant T315I. These results indicate that the function of CRKL as an adapter protein is essential for p210BCR-ABL–induced transformation. Cancer Res; 70(18); 7325–35. ©2010 AACR.Keywords
This publication has 58 references indexed in Scilit:
- Structural and Functional Basis of a Role for CRKL in a Fibroblast Growth Factor 8-Induced Feed-Forward LoopMolecular and Cellular Biology, 2009
- Crkl Deficiency Disrupts Fgf8 Signaling in a Mouse Model of 22q11 Deletion SyndromesDevelopmental Cell, 2006
- T cell development and function in CrkL‐deficient miceEuropean Journal of Immunology, 2003
- A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemiasBlood, 2002
- BCR/ABL P190 transgenic mice develop leukemia in the absence of CrklOncogene, 2002
- A peptide carrier for the delivery of biologically active proteins into mammalian cellsNature Biotechnology, 2001
- Development of highly selective SH3 binding peptides for Crk and CRKL which disrupt Crk-complexes with DOCK180, SoS and C3GOncogene, 1998
- Tyrosine 207 in CRKL is the BCR/ABL phosphorylation siteOncogene, 1997
- Differential Complementation of Bcr-Abl Point Mutants with c-MycScience, 1994
- The Molecular Genetics of Philadelphia Chromosome–Positive LeukemiasNew England Journal of Medicine, 1988