BCR/ABL and Signal Transduction Pathways

作者: R. Salgia , K. Okuda , N. Carlesso , J. D. Griffin

DOI: 10.1007/978-3-642-60377-8_26

关键词: Cell biologyIntegrinCRKLbreakpoint cluster regionGRB2ABLSH3 domainHaematopoiesisChemistrySignal transduction

摘要: BCR/ABL transforms hematopoietic cells in vitro and vivo exerts a wide variety of biological effects, including induction factor independence, reduction apoptosis, altering adhesion CML to marrow stroma. However, at biochemical level, the mechanisms by which myeloid are poorly understood. p210BCR/ABL has elevated ABL tyrosine kinase activity, relocates cytoskeleton, phosphorylates several cellular proteins, c-BCR, pl20rasGAP, c-CBL, p52SHC, p93FES, p95VAV, pl25FAK, p68paxillin, p72SH PTP2. In addition, been shown bind directly GRB2 Y177 BCR, therefore potentially activating p21ras. it difficult determine significance any these potential substrates, part due complexity studying large protein with many signaling motifs, fact that there so substrates cell lines. One approach simplifying biology examine primary human cells, rather than lines made overexpress BCR/ABL. Interestingly, leukemic only few proteins either intereact or phosphorylated This suggests studies tissue culture lines, may be more reliable terms identifying important pathways. major phosphoproteins complexed neutrophils recently identified as CRKL, an SH2/SH3 “adapter” protein. CRKL binds least partly through its SH3 domain, link some cytoskeletal proteins. The hypothesis is set forth functions disrupt signals going to, coming from integrins this event pathogenesis stable phase CML.

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