scholarly journals Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding.

1994 ◽  
Vol 14 (12) ◽  
pp. 8432-8437 ◽  
Author(s):  
B Tang ◽  
H Mano ◽  
T Yi ◽  
J N Ihle
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Amino Terminal ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.

scholarly journals Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding

1994 ◽  
Vol 14 (12) ◽  
pp. 8432-8437
Author(s):  
B Tang ◽  
H Mano ◽  
T Yi ◽  
J N Ihle
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Amino Terminal ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.

Phase I Study of Chimeric Human/Murine Anti–Ganglioside GD2Monoclonal Antibody (ch14.18) With Granulocyte-Macrophage Colony-Stimulating Factor in Children With Neuroblastoma Immediately After Hematopoietic Stem-Cell Transplantation: A Children’s Cancer Group Study

2000 ◽  
Vol 18 (24) ◽  
pp. 4077-4085 ◽  
Author(s):  
M. Fevzi Ozkaynak ◽  
Paul M. Sondel ◽  
Mark D. Krailo ◽  
Jacek Gan ◽  
Brad Javorsky ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Neuroblastoma Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE: Ganglioside GD2is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-GD2monoclonal antibody (ch14.18) can induce lysis of neuroblastoma cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The purposes of the study were (1) to determine the maximum-tolerated dose (MTD) of ch14.18 in combination with standard dose granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with neuroblastoma who recently completed hematopoietic stem-cell transplantation (HSCT), and (2) to determine the toxicities of ch14.18 with GM-CSF in this setting.PATIENTS AND METHODS: Patients became eligible when the total absolute phagocyte count (APC) was greater than 1,000/μL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 μg/m2/d starting at least 3 days before ch14.18 and continued for 3 days after the completion of ch14.18. The ch14.18 dose levels were 20, 30, 40, and 50 mg/m2/d. In the absence of progressive disease, patients were allowed to receive up to six 4-day courses of ch14.18 therapy with GM-CSF. Nineteen patients with neuroblastoma were treated.RESULTS: A total of 79 courses were administered. No toxic deaths occurred. The main toxicities were severe neuropathic pain, fever, nausea/vomiting, urticaria, hypotension, mild to moderate capillary leak syndrome, and neurotoxicity. Three dose-limiting toxicities were observed among six patients at 50 mg/m2/d: intractable neuropathic pain, grade 3 recurrent urticaria, and grade 4 vomiting. Human antichimeric antibody developed in 28% of patients.CONCLUSION: ch14.18 can be administered with GM-CSF after HSCT in patients with neuroblastoma with manageable toxicities. The MTD is 40 mg/m2/d for 4 days when given in this schedule with GM-CSF.

scholarly journals Cell-to-cell interaction of cytokine-dependent myeloblastic line constitutively expressing membrane-bound stem cell factor abrogates cytokine dependency partially through granulocyte-macrophage colony- stimulating factor production

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1220-1228 ◽  
Author(s):  
K Sasaki ◽  
K Ikeda ◽  
K Ogami ◽  
J Takahara ◽  
S Irino
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Cell Interaction ◽  
Colony Stimulating Factor ◽  
Semisolid Medium ◽  
Gm Csf ◽  
Membrane Bound ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Stem cell factor (SCF) is a cytokine for hematopoietic progenitor cells and plays an important role in megakaryocyte proliferation. The UT-7 cell line was established from a patient with megakaryoblastic leukemia, and its growth and survival are strictly dependent on interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), or IL-6. In this study, we showed that SCF also supported the growth of UT-7 in the absence of other cytokines and downregulated the cell surface c-kit receptors. Constitutive expression of SCF by introducing SCF expression vector made UT-7 grow factor-independently in liquid medium, but not in semisolid medium. This SCF-expressing factor-independent UT-7 (UT-7scf9) expressed the membrane bound form of SCF on their surface, but did not secrete detectable amounts of soluble SCF. UT-7scf9 formed aggregates as they grew in the absence of cytokines, and this aggregation was inhibited by adding soluble SCF into the medium. UT-7 cultured with SCF and UT-7scf9 cultured without cytokines expressed GM-CSF, and anti-GM-CSF neutralizing antibody partially inhibited their growth. These results suggest that SCF stimulated UT-7 proliferation partially through the autocrine-loop of GM-CSF, and UT-7scf9 expressed SCF mostly as a membrane-bound form, which transduces its growth signal through c-kit receptor as they aggregate by cell-to-cell interaction.

Serum Levels of Granulocyte-Macrophage-colony-stimulating Factor and Stem-cell Factor During Liver Regeneration after Partial Hepatectomy in Humans

2020 ◽  
Vol 15 (2) ◽  
pp. 131-136
Author(s):  
Diego Fiume ◽  
Ilaria Lenci ◽  
Martina Milana ◽  
Tommaso M. Manzia ◽  
Renato Massoud ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Regeneration ◽  
Liver Tumor ◽  
Stem Cell Factor ◽  
Serum Levels ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Background: Multiple biological functions have been recognized regarding Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Stem Cell Factor (SCF). Aim: To evaluate the serum changes of GM-CSF and SCF in patients undergoing surgical resection for liver tumor, in the regenerative phase after surgery in order to identify the possible relationship with the patient, tumor or surgical variables. Methods: Thirty-two consecutive patients (50% male, median age 66), undergoing hepatic resection of liver neoplasm, were evaluated. The liver tumor was Hepatocellular Carcinoma (HCC) in 44% of cases. Other tumors were cholangiocarcinoma and metastasis. Serum levels of GM-CSF and SCF were assessed at baseline and 2 days, 7 days and 4 weeks after surgery. Personal and clinical patient data were also recorded. The statistical analysis was carried out using t-test for unpaired data or ANOVA (repeated measure) for continuous variables and Fisher test for discrete variables. Results: GM-CSF levels remained constant after surgery and were compared to baseline values. SCF levels, on the other hand, increased during the time, after surgery. The evaluation of SCF levels (fold increase) according to surgical, patient and tumor variables evidenced some differences. At day 7 and week 4, SCF levels were statistically increased: i) in patients undergoing a large resection in comparison with others (p<0.05); ii) in patients non-cirrhotic in comparison with cirrhotic ones (p=0.02) and finally; iii) in patients with non-HCC tumor in comparison with HCC ones (p=0.02). Conclusions: During liver regeneration in humans, SCF serum levels are increased allowing to hypothesize a possible role of this chemokine during tissue growth and remodeling.

Secretion of stem cell factor and granulocyte–macrophage colony-stimulating factor by mouse embryos in culture: influence of group culture

Zygote ◽  
2008 ◽  
Vol 16 (4) ◽  
pp. 297-301 ◽  
Author(s):  
A. P. Contramaestre ◽  
F. Sifontes ◽  
R. Marín ◽  
M. I. Camejo
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Culture Medium ◽  
Mouse Embryos ◽  
Colony Stimulating Factor ◽  
Group Culture ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

SummaryPrevious studies showed that the addition of a growth factor to the culture medium could modulate embryo development. The possible secretion of different factors to the culture medium by the embryo itself, however, has been poorly evaluated. The present study was designed to investigate: (1) the influence of single or group culture on the development of 2-cell mouse embryos (strain CD-1) to the blastocyst stage; (2) the release of granulocyte–macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) into the culture medium by the embryo; and (3) the levels of GM-CSF and SCF in the culture medium from both single and group embryos. Two-cell CD-1 mouse embryos were cultured for 96 h singly or in groups of five embryos per drop. GM-CSF and SCF were assayed by ELISA in the complete culture medium. It was found that embryos cultured in groups gave a higher percentage of total blastocyst formation and hatched blastocyst when compared with single embryo culture. The mouse embryos secreted GM-CSF and SCF to the culture medium. The concentration of these cytokines is significantly higher in the group cultures than the level found in single cultures. In conclusion, mouse embryos in culture secrete GM-CSF and SCF to the culture medium and the concentration of these cytokines increases during communal culture. These factors may be operating in both autocrine and paracrine pathways to modulate embryo development during in vitro culture.

scholarly journals Cytokine Receptor Expression on Hematopoietic Stem and Progenitor Cells

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 65-71 ◽  
Author(s):  
William J. McKinstry ◽  
Chung-Leung Li ◽  
John E.J. Rasko ◽  
Nicos A. Nicola ◽  
Gregory R. Johnson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Population ◽  
Progenitor Cell ◽  
Cell Populations ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Hematopoietic stem and progenitor cell populations were obtained by fluorescence activated cell sorting of murine bone marrow (BM) cells into Rhodamine-123lo lineage−Ly6A/E+ c-kit+ (primitive stem cells highly enriched for long-term BM repopulating activity), Rhodamine-123med/hi lineage− Ly6A/E+ c-kit+ (mature stem cells highly enriched for short-term BM repopulating activity and day 13 spleen colony-forming activity) and lineage− Ly6A/E− c-kit+ (enriched for in vitro colony forming cells) populations. Neither stem cell population responds to single cytokines in vitro and each requires the synergistic action of two or more cytokines for proliferation, whereas the progenitor cell population proliferates in response to single cytokines. Since each of these cell populations was sorted as c-kit+, they express receptors for stem cell factor. Cell populations were also analyzed by autoradiography for their ability to specifically bind iodinated cytokines and this revealed that both stem cell populations expressed receptors for interleukin-1α (IL-1α), IL-3, IL-6, and granulocyte colony-stimulating factor (G-CSF ), but lacked receptors for macrophage colony-stimulating factor (M-CSF ), granulocyte-macrophage colony stimulating factor (GM-CSF ), and leukemia inhibitory factor (LIF ). Cells within the progenitor cell population specifically bound IL-3, GM-CSF, G-CSF, IL-6, and IL-1α, whereas no receptors were detected for M-CSF and LIF. Within each cell population examined, heterogeneity was observed in the percentage of cells labeled and the number of receptors per cell. These results suggest that stem cell populations can be further subdivided according to their cytokine receptor profile and it will be of interest to determine if such subpopulations have distinctive functional properties.

Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis after hematopoietic stem-cell transplantation.

1994 ◽  
Vol 12 (9) ◽  
pp. 1917-1922 ◽  
Author(s):  
B Gordon ◽  
A Spadinger ◽  
E Hodges ◽  
E Ruby ◽  
R Stanley ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Oral Mucositis ◽  
Airway Compromise ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

PURPOSE Oral mucositis following high-dose chemotherapy may result in systemic infection and airway compromise, and the severity of oral mucositis may be dose-limiting. Here we investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), which significantly shortens duration of neutropenia after hematopoietic stem-cell transplantation (HSCT) on oral mucositis. PATIENTS AND METHODS Thirteen children undergoing HSCT were prepared with etoposide (VP-16), thiotepa (TT), and total-body irradiation (TBI), and 13 with VP-16, TT, and cyclophosphamide (CPM). Following transplantation, 14 patients received GM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion (six prepared with VP-16, TT, and TBI, and eight prepared with VP-16, TT, and CPM), and 12 patients received no growth factor. RESULTS Mucositis was more severe and persisted longer in patients prepared with the TBI-containing regimen. For this regimen, the duration of severe oral mucositis was shortened by the administration of GM-CSF, although the severity of mucositis was unaffected. No statistically significant effect of GM-CSF could be shown in patients who received VP-16, TT, and CPM. The incidence of positive fungal oral or blood cultures did not appear different whether patients received GM-CSF or not. CONCLUSION For patients undergoing stomatotoxic HSCT regimens, GM-CSF may reduce the duration of oral mucositis, but is unlikely to effect the severity of oral mucositis or risk of airway compromise, and the severity of mucositis is likely to remain dose-limiting.

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