Lu D, Liu J, Campbell M, Guo J Q, Heisterkamp N, Groffen J, Canaani E, Arlinghaus R
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Blood. 1993 Aug 15;82(4):1257-63.
It is well established that the chimeric BCR-ABL gene formed by joining parts of the BCR and ABL genes plays a key role in the pathogenesis of Philadelphia (Ph) chromosome-positive leukemias. We report that simultaneous expression of P210 BCR-ABL and P160 BCR in simian COS-1 cells yielded stable complexes of these two proteins, and induced phosphorylation of P160 BCR on tyrosine residues in vivo. Tyrosine phosphorylation of a deletion mutant encoding 553 amino acids of BCR N-terminal sequences was also detected when it was coexpressed with P210 BCR-ABL. We propose that tyrosine phosphorylation of P160 BCR by P210 BCR-ABL and their stable physical interaction may perturb normal BCR functions and that these alterations are directly involved in the pathologic processes found in Ph chromosome-associated leukemias.
众所周知，由BCR基因和ABL基因部分连接形成的嵌合BCR-ABL基因在费城（Ph）染色体阳性白血病的发病机制中起关键作用。我们报告，在猿猴COS-1细胞中同时表达P210 BCR-ABL和P160 BCR可产生这两种蛋白质的稳定复合物，并在体内诱导P160 BCR酪氨酸残基的磷酸化。当编码BCR N端序列553个氨基酸的缺失突变体与P210 BCR-ABL共表达时，也检测到其酪氨酸磷酸化。我们提出，P210 BCR-ABL对P160 BCR的酪氨酸磷酸化及其稳定的物理相互作用可能会扰乱正常的BCR功能，并且这些改变直接参与了Ph染色体相关白血病中的病理过程。
