Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation
Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation
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DOI：
10.1038/sj.leu.2402214
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发表时间：
2001-09-01
期刊：
影响因子：
11.4
通讯作者：
Lorenz, U
中科院分区：
文献类型：
--
作者：
Bruecher-Encke, B;Griffin, JD;Lorenz, U
红-巨核细胞白血病细胞系K562在各种诱导剂处理后发生红系或骨髓分化。我们观察到，含SH 2的蛋白酪氨酸磷酸酶SHP-1的表达诱导后，暴露的K562细胞分化剂。在相同的条件下，SHP-1的近亲SHP-2和更远的PTP-1B的表达保持不变。诱导SHP-1的表达与一组特定的和有限的酪氨酰磷蛋白的去磷酸化相关，这表明这些蛋白的去磷酸化对分化过程可能是重要的。重要的是，外源性SHP-1的表达抑制K562增殖并改变这些细胞的粘附特性，表明更分化的表型。此外，发现SHP-1与p210 Bcr-Abl和p190 Bcr-Abl复合，表明它可能调节Bcr-Abl或Bcr-Abl相关的磷酸酪氨酸蛋白。我们的研究结果表明，诱导SHP-1的表达是重要的K562分化在各种诱导剂和提高的可能性，SHP-1的功能失活可能发挥作用，在慢性粒细胞白血病急变的进展。
The erythro-megakaryoblastic leukemia cell line K562 undergoes erythroid or myeloid differentiation in response to treatment with various inducing agents. We observed that expression of the SH2-containing protein tyrosine phosphatase SHP-1 was induced upon exposure of K562 cells to differentiating agents. Under the same conditions, expression of SHP-2, a close relative of SHP-1, and the more distantly related PTP-1B remained unchanged. Induction of SHP-1 expression correlates with dephosphorylation of a specific and limited set of tyrosyl phosphoproteins, suggesting that dephosphorylation of these proteins may be important for the differentiation process. Importantly, expression of exogenous SHP-1 inhibits K562 proliferation and alters the adhesion properties of these cells, indicating a more differentiated phenotype. Moreover, SHP-1 is found in a complex with both p210 Bcr-Abl and p190 Bcr-Abl, suggesting that it may regulate Bcr-Abl or Bcr-Abl-associated phosphotyrosyl proteins. Our results indicate that induction of SHP-1 expression is important for K562 differentiation in response to various inducers and raise the possibility that functional inactivation of SHP-1 may play a role in progression to blast crisis in chronic myelogenous leukemia.