Panopoulos Athanasia D, Bartos David, Zhang Ling, Watowich Stephanie S
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
J Biol Chem. 2002 May 24;277(21):19001-7. doi: 10.1074/jbc.M112271200. Epub 2002 Mar 11.
Granulocyte colony-stimulating factor (G-CSF) plays an essential role in regulating multiple aspects of hematopoiesis. To elucidate the role of G-CSF in controlling hematopoietic cell migration capabilities, we studied inducible expression of the myeloid-specific marker, integrin alpha(M)beta(2) (CD11b/CD18, Mac-1), in the myeloid cell line, 32D. We found that G-CSF stimulates the synthesis and cell surface expression of alpha(M) and beta(2) integrin subunits. Induction of both alpha(M) and beta(2) is dependent on Stat3, a major G-CSF-responsive signaling protein. However, the kinetics of expression suggested the involvement of an intermediate protein regulated by Stat3. Our results demonstrate that Stat3 signaling stimulates the expression of PU.1, a critical regulator of myelopoiesis. Furthermore, we show that PU.1 is an essential intermediate for the inducible expression of alpha(M)beta(2) integrin. Thus, Stat3 promotes alpha(M)beta(2) integrin expression through its activation of PU.1. These findings indicate that G-CSF-dependent Stat3 signals stimulate the changes in cell adhesion and migration capabilities that occur during myeloid cell development. These data also demonstrate a link between Stat3 and PU.1, suggesting that Stat3 may play an instructive role in hematopoiesis.
粒细胞集落刺激因子（G-CSF）在调节造血的多个方面发挥着重要作用。为了阐明G-CSF在控制造血细胞迁移能力中的作用，我们研究了髓系特异性标志物整合素α(M)β(2)（CD11b/CD18，Mac-1）在髓系细胞系32D中的诱导表达。我们发现G-CSF刺激α(M)和β(2)整合素亚基的合成及细胞表面表达。α(M)和β(2)的诱导均依赖于Stat3，Stat3是一种主要的G-CSF反应性信号蛋白。然而，表达动力学提示存在一种受Stat3调节的中间蛋白参与其中。我们的结果表明，Stat3信号传导刺激髓系造血关键调节因子PU.1的表达。此外，我们表明PU.1是α(M)β(2)整合素诱导表达所必需的中间物。因此，Stat3通过激活PU.1促进α(M)β(2)整合素的表达。这些发现表明，G-CSF依赖的Stat3信号刺激髓系细胞发育过程中发生的细胞黏附和迁移能力的变化。这些数据还证明了Stat3与PU.1之间的联系，表明Stat3可能在造血过程中发挥指导作用。
