TY - JOUR AB - The BCR-ABL fusion protein is strongly implicated in the malignant process of Philadelphia (Ph-1)-positive leukemia. The BCR-ABL fusion protein exhibits a deregulated tyrosine kinase activity capable of phosphorylating different cellular substrates in vivo and in vitro. SHP-1 (SHPTP1, PTP1C, HCP, SHP) is an SH2 domain-containing tyrosine phosphatase expressed predominantly in hematopoietic cells. The association of the murine motheaten phenotype of severe hematopoietic dysregulation with loss of SHP-1 tyrosine phosphatase activity indicates a critical role of SHP-1 in the regulation of hematopoietic cell growth and differentiation. Experiments were performed to determine whether SHP-1 might form specific complexes with BCR-ABL signaling pathway. We found that SHP-1 was highly and constitutively tyrosine phosphorylated in 32DCl3 and TF-1 cells transfected with BCR-ABL expression vector. Furthermore, SHP-1 and BCR-ABL formed stable complexes in BCR-ABL expressing cells. Direct binding between SHP-1 and Grb2 was observed in vitro. Expression of BCR-ABL in TF-1 cells resulted in a two-fold increase in SHP-1 phosphatase activity. BCR-ABL tyrosine kinase was able to phosphorylate recombinant SHP-1 protein in vitro. SHP-1 therefore has the capacity to bind and potentially modulate the signaling effectors involved in activation of Ras, and accordingly, regulation of cellular transformation of BCR-ABL. AD - KYOWA HAKKO KOGYO CO LTD,TOKYO RES LABS,TOKYO 194,JAPAN. AU - Tauchi,T AU - Ohyashiki,K AU - Yamashita,Y AU - Sugimoto,S AU - Toyama,K DA - 1997/09/01 DO - 10.3892/ijo.11.3.471 EP - 475 IS - 3 JO - Int J Oncol PY - 1997 SN - 1019-6439 1791-2423 SP - 471 ST - SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways T2 - International Journal of Oncology TI - SH2-containing phosphotyrosine phosphatase SHP-1 is involved in BCR-ABL signal transduction pathways UR - https://doi.org/10.3892/ijo.11.3.471 VL - 11 ER -