Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin

Miller, BA; Foster, Karen; Robishaw, JD; Whitfield, CF; Bell, Laurie; Cheung, JY

doi:10.1182/blood.v77.3.486.bloodjournal773486

Cited by 2 publications

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“…The intracellular cAMP level was increased by addition of Epo in mouse erythroleukemia SKT6 cells (20) and BFU-E-derived erythroblasts (24) but not in Epodependent clone of DA-1 (DA-1ER) (36) and murine erythroleukemia cells (TSA8) (10). Epo may also have the ability to increase the intracellular cAMP level in other kinds of cells.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells

Ito

Kusano²,

Furukawa

et al. 2002

American Journal of Physiology-Cell Physiology

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We previously reported that erythropoietin (Epo) has a mitogenic effect on rat vascular smooth muscle cells (VSMC) and that activation of the mitogen-activated protein kinase (MAPK) cascade is an important mediator for Epo-induced mitogenesis. An increase in intracellular cAMP has an antiproliferative effect on VSMC. We therefore hypothesized that cAMP effectors inhibit Epo-induced MAPK activation in rat VSMC. When we exposed VSMC to recombinant human Epo (rHuEpo), DNA synthesis was increased. Forskolin (Fsk) or cilostazol (Cil) decreased the DNA synthesis stimulated by rHuEpo. Coincubation with Rp-cAMPS triethylamine canceled the suppression of DNA synthesis and MAPK activity by Fsk. Both rHuEpo and phorbol 12-myristate 13-acetate upregulated phosphorylations of MEK and MAPK. Pretreatment with Fsk inhibited these phosphorylations. Protein kinase C inhibitors also suppressed MEK and MAPK phosphorylations. Moreover, Fsk induced phosphorylation of Raf-1 at serine-259. These results indicated that cAMP inhibited Epo-induced MAPK activation and that this suppression might be regulated upstream or at Raf-1. The results also suggested that these agents, which could accumulate cAMP, might be protective for Epo-stimulated direct action.

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Section: Discussionmentioning

confidence: 99%

Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells

Ito

Kusano²,

Furukawa

et al. 2002

American Journal of Physiology-Cell Physiology

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Regulation by Gi2 proteins of v-fms-induced proliferation and transformation via Src-kinase and STAT3

1999

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We previously showed that G i2 proteins interfere with the transduction of CSF-1 receptor (CSF-1R) proliferation signals (Corre and Hermouet, 1995). To identify CSF-1R pathways controlled by G i2 , we transfected v-fms, the oncogenic equivalent of CSF-1R, in NIH3T3 cells in which G i2 proteins were inactivated by stably expressing a dominant negative mutant form of the a subunit of G i2 (a i2 -G204A). Expression of a i2 -G204A resulted in decreased Src-kinase activity, delayed activation of p42 ERK-MAPK, decreased cyclin D1 expression and reduced proliferation in response to serum. In a i2 -G204A cells transfected with v-fms, Src-kinase activity remained de®cient but p42 MAPK activity and cyclin D1 expression were similar to those of vector/v-fms cells, suggesting that v-fms bypasses Src to activate the ERK-MAPK cascade. However, DNA synthesis and focus formation were inhibited by up to 80% in a i2 -G204A/vfms cells compared to vector/v-fms cells. We found that tyrosine phosphorylation of STAT3, also activated by CSF-1R/v-fms, was inhibited in a i2 -G204A/v-fms cells; in addition, expression of an 85 kDa, C-terminal truncated form of STAT3 (STAT3D) was constitutively increased. Both the inhibition of v-fms-induced STAT3 tyrosine phosphorylation and the increased expression of STAT3D were reproduced by transfecting a dominant negative mutant of Src. Last, we show that expression of STAT3D55C, a mutant form of STAT3 lacking the last 55 C-terminal amino acids, is su cient to inhibit DNA synthesis and v-fms-induced transformation in NIH3T3 cells. In summary, adequate regulation by G i2 proteins of the activity of both Src-kinase and STAT3 is required for optimal cell proliferation in response to CSF-1R/vfms.

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Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin

Cited by 2 publications

References 0 publications

Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells

Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells

Regulation by Gi2 proteins of v-fms-induced proliferation and transformation via Src-kinase and STAT3

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