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- Title
Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR/ABL-transformed cells.
- Authors
Sattler, M; Salgia, R
- Abstract
CRKL is a 39 kDa adapter protein, originally cloned in proximity to the BCR gene on chromosome 22, which has a key regulatory role in hematopoietic cells. CRKL has one SH2 and two SH3 domains, with 60% homology to CRK II. CRKL is a prominent substrate of the BCR/ABL oncoprotein in chronic myelogenous leukemia and binds to both BCR/ABL and c-ABL. CRKL has been shown to be tryosine phosphorylated in response to normal hematopoietic growth factor receptor signaling with ligands such as thrombopoietin, erythropoietin or steel factor. Additionally, CRKL is involved in signaling initiated by crosslinking of beta integrins, and B cell or T cell receptors. Structurally, the amino-terminal SH3 domain of CRKL has been shown to bind proteins such as C3G, SOS, PI3-K, c-ABL or BCR/ABL. The SH2 domain of CRKL can bind to tyrosine phosphorylated proteins such as CBL, HEF1, CAS or paxillin. This review summarizes the current knowledge on the function of this unique adapter protein in normal hematopoietic and leukemic cell signaling.
- Subjects
PROTEINS; CHROMOSOMES; BLOOD cells; PROTEIN metabolism; AMINO acids; ANIMAL experimentation; CARRIER proteins; CELLS; CELLULAR signal transduction; COMPARATIVE studies; DOCUMENTATION; HEMATOPOIETIC stem cells; RESEARCH methodology; MEDICAL cooperation; RESEARCH; EVALUATION research; NUCLEAR proteins
- Publication
Leukemia (08876924), 1998, Vol 12, Issue 5, p637
- ISSN
0887-6924
- Publication type
journal article
- DOI
10.1038/sj.leu.2401010