Polycythemia vera. V. Enhanced proliferation and phosphorylation due to vanadate are diminished in polycythemia vera erythroid progenitor cells: a possible defect of phosphatase activity in polycythemia vera.
Polycythemia vera. V. Enhanced proliferation and phosphorylation due to vanadate are diminished in polycythemia vera erythroid progenitor cells: a possible defect of phosphatase activity in polycythemia vera.
复制标题
真性红细胞增多症。
作者：
C. Dai;S. B. Krantz;S. T. Sawyer
在无血清培养条件下，促红细胞生成素(EP)和干细胞因子(SCF)是红系祖细胞增殖和分化所必需的生长因子。此前已有研究表明，真性红细胞增多症(PV)患者的红系祖细胞--红系和集落形成单位--与正常红系祖细胞相比，对EP和SCF的敏感性增强，但其机制尚不清楚。本文研究了EP和SCF对正常和PV红系集落形成细胞的蛋白质酪氨酸磷酸化的影响，以形成2-49个血红化细胞集落。EP迅速诱导EP受体的酪氨酸磷酸化，而SCF诱导的最显著的磷酸化蛋白是SCF受体。当PV细胞与正常细胞相比时，没有明显的额外的磷酸化蛋白。用蛋白酪氨酸磷酸酶的抑制剂原钒酸盐培养正常的红系祖细胞，可导致红系集落数量增加和蛋白酪氨酸磷酸化增强。然而，相比之下，光伏细胞几乎没有明显的增强作用。这些结果表明，虽然在正常的红系祖细胞中，钒可能作为一种磷酸酶抑制剂，增强了SCF和EP诱导的激酶活性，但在PV细胞中，这一功能被减弱。由于红细胞生成受蛋白酪氨酸激酶活性和蛋白酪氨酸磷酸酶活性之间的平衡调节，因此PV患者可能存在异常的磷酸酶活性，从而导致细胞增殖增加。
Erythropoietin (EP) and stem cell factor (SCF) are essential growth factors for erythroid progenitor cell proliferation and differentiation in serum-free culture. It has been previously shown that burst-forming units-erythroid and colony-forming units-erythroid from patients with polycythemia vera (PV) have enhanced sensitivity to EP and SCF compared with normal erythroid progenitors, but little is known about the mechanism for this difference. In the present investigation, the effect of EP and SCF on protein tyrosine phosphorylation in day-8 normal and PV erythroid colony-forming cells, which give rise to colonies of 2-49 hemoglobinized cells, was studied. EP rapidly induced tyrosine phosphorylation of the EP receptor, whereas the most prominent phosphorylated protein induced by SCF was identified as the SCF receptor. No additional phosphorylated proteins were evident when PV cells were compared with normal cells. Culture of normal erythroid progenitors with orthovanadate, an inhibitor of protein tyrosine phosphatases, resulted in an increased number of erythroid colonies and enhanced protein tyrosine phosphorylation. However, in contrast, little enhancement was evident with PV cells. These results indicate that, although vanadate may be acting in normal erythroid progenitors as a phosphatase inhibitor that potentiates the kinase activity induced by SCF and EP, this function is diminished in PV cells. Because erythropoiesis is regulated by a balance between protein tyrosine kinase activity and protein tyrosine phosphatase activity, PV patients may have an abnormal phosphatase activity allowing increased cell proliferation.
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DOI：
10.1073/pnas.90.14.6849
发表时间：
1993-07-15
影响因子：
11.1
作者：
SAWYER, ST;HANKINS, WD
通讯作者：
HANKINS, WD
鼠肥大细胞生长因子（c-kit原癌基因配体）对人骨髓造血祖细胞集落形成的影响。
影响因子：
20.3
作者：
Broxmeyer,HE;Cooper,S;Lu,L;Hangoc,G;Anderson,D;Cosman,D;Lyman,SD;Williams,DE
通讯作者：
Williams,DE
免疫缺陷小鼠突变体的血液学异常，可存活的受害小鼠（mev）。
影响因子：
2.6
作者：
VanZant,G;Shultz,L
通讯作者：
Shultz,L
影响因子：
15.9
作者：
MUTA, K;KRANTZ, SB;WICKREMA, A
通讯作者：
WICKREMA, A
重组人白细胞介素 9 诱导蛋白质酪氨酸磷酸化，并与钢因子协同作用，刺激人因子依赖性细胞系 M07e 的增殖。
影响因子：
20.3
作者：
Miyazawa,K;Hendrie,PC;Kim,YJ;Mantel,C;Yang,YC;Kwon,BS;Broxmeyer,HE
通讯作者：
Broxmeyer,HE