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Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling.

Zhang S, Fukuda S, Lee Y, Hangoc G, Cooper S, Spolski R, Leonard WJ, Broxmeyer HE - J. Exp. Med. (2000)

Bottom Line: Interestingly, FL did not activate any Jaks.A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a(-/-) mice, but did stimulate/costimulate proliferation of these cells from Stat5a(+/+), Stat5b(-/-), and Stat5b(+/+) mice.Thus, Stat5a is essential for at least certain effects of FL.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

ABSTRACT
The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic stem and progenitor cells. Although some post-receptor signaling events of Flt3 have been characterized, the involvement of the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in Flt3 signaling has not been thoroughly evaluated. To this aim, we examined whether Flt3 activates the Jak/Stat pathway in Baf3/Flt3 cells, a line stably expressing human Flt3 receptor. Stat5a, but not Stats 1-4, 5b, or 6, was potently activated by Flt3 ligand (FL) stimulation. Interestingly, FL did not activate any Jaks. Activation of Stat5a required the kinase activity of Flt3. A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a(-/-) mice, but did stimulate/costimulate proliferation of these cells from Stat5a(+/+), Stat5b(-/-), and Stat5b(+/+) mice. Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.

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FL stimulates/costimulates proliferation of myeloid progenitor cells from marrows of Stat5b+/+ and Stat5b−/− mice to the same extent. Results are shown as the average percentage of control of cells incubated with 50 ng/ml SLF plus 10 ng/ml GM-CSF for a total of two experiments each. The control colony numbers upon which the percentage of control are based were 66 ± 2 and 93 ± 1 for Stat5b−/− cells, and 93 ± 2 and 74 ± 3 for Stat5b+/+ cells.
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Figure 7: FL stimulates/costimulates proliferation of myeloid progenitor cells from marrows of Stat5b+/+ and Stat5b−/− mice to the same extent. Results are shown as the average percentage of control of cells incubated with 50 ng/ml SLF plus 10 ng/ml GM-CSF for a total of two experiments each. The control colony numbers upon which the percentage of control are based were 66 ± 2 and 93 ± 1 for Stat5b−/− cells, and 93 ± 2 and 74 ± 3 for Stat5b+/+ cells.

Mentions: To evaluate the specificity of these effects, similar comparative experiments were done with myeloid progenitor cells from Stat5b−/− and their littermate control Stat5b+/+ mice (Fig. 7). No significant differences (P > 0.05) were noted in the responses of Stat5b−/− and Stat5b+/+ cells to the individual effects of FL, SLF, GM-CSF, M-CSF, G-CSF, or to the combined effects of SLF or FL with each other or with any of the CSFs. At the same time these experiments were done, experiments were also done with Stat5a−/− and Stat5a+/+ cells with results comparable to those seen in Fig. 6.


Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling.

Zhang S, Fukuda S, Lee Y, Hangoc G, Cooper S, Spolski R, Leonard WJ, Broxmeyer HE - J. Exp. Med. (2000)

FL stimulates/costimulates proliferation of myeloid progenitor cells from marrows of Stat5b+/+ and Stat5b−/− mice to the same extent. Results are shown as the average percentage of control of cells incubated with 50 ng/ml SLF plus 10 ng/ml GM-CSF for a total of two experiments each. The control colony numbers upon which the percentage of control are based were 66 ± 2 and 93 ± 1 for Stat5b−/− cells, and 93 ± 2 and 74 ± 3 for Stat5b+/+ cells.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193267&req=5

Figure 7: FL stimulates/costimulates proliferation of myeloid progenitor cells from marrows of Stat5b+/+ and Stat5b−/− mice to the same extent. Results are shown as the average percentage of control of cells incubated with 50 ng/ml SLF plus 10 ng/ml GM-CSF for a total of two experiments each. The control colony numbers upon which the percentage of control are based were 66 ± 2 and 93 ± 1 for Stat5b−/− cells, and 93 ± 2 and 74 ± 3 for Stat5b+/+ cells.
Mentions: To evaluate the specificity of these effects, similar comparative experiments were done with myeloid progenitor cells from Stat5b−/− and their littermate control Stat5b+/+ mice (Fig. 7). No significant differences (P > 0.05) were noted in the responses of Stat5b−/− and Stat5b+/+ cells to the individual effects of FL, SLF, GM-CSF, M-CSF, G-CSF, or to the combined effects of SLF or FL with each other or with any of the CSFs. At the same time these experiments were done, experiments were also done with Stat5a−/− and Stat5a+/+ cells with results comparable to those seen in Fig. 6.

Bottom Line: Interestingly, FL did not activate any Jaks.A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a(-/-) mice, but did stimulate/costimulate proliferation of these cells from Stat5a(+/+), Stat5b(-/-), and Stat5b(+/+) mice.Thus, Stat5a is essential for at least certain effects of FL.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

ABSTRACT
The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic stem and progenitor cells. Although some post-receptor signaling events of Flt3 have been characterized, the involvement of the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in Flt3 signaling has not been thoroughly evaluated. To this aim, we examined whether Flt3 activates the Jak/Stat pathway in Baf3/Flt3 cells, a line stably expressing human Flt3 receptor. Stat5a, but not Stats 1-4, 5b, or 6, was potently activated by Flt3 ligand (FL) stimulation. Interestingly, FL did not activate any Jaks. Activation of Stat5a required the kinase activity of Flt3. A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a(-/-) mice, but did stimulate/costimulate proliferation of these cells from Stat5a(+/+), Stat5b(-/-), and Stat5b(+/+) mice. Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.

Show MeSH
Related in: MedlinePlus