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Pfeilstöcker, M; Karlic, H; Paukovits, J; Anzenberger, G; Louda, N; Salamon, J; Mühlberger, H; Strobl, H; Pittermann, E; Heinz, R.
In vivo and in vitro effects of cytokines and the hemoregulatory peptide dimer (pEEDCK)2 (pyroGlu-Glu-Asp-Cys-Lys)2 on G alpha16-positive hematopoiesis.
Leukemia. 1999; 13(4):590-594
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Autor/innen der Med Uni Graz:
Strobl Herbert
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Abstract:
G proteins play an important role in signal transduction from cytokine receptors to intracellular effectors via different pathways, eg involving tyrosine kinases. In our previous studies, we demonstrated that mRNA expression of the hematopoiesis-specific G protein alpha-subunit G alpha16 is a sensitive marker indicating the appearance of early myeloid and lymphoid progenitors. This study was designed to investigate cytokine effects on hematopoiesis in vivo and in vitro as reflected by G alpha16 expression and sensitivity to the hemoregulatory peptide (pEEDCK)2 which harbors a structural homology to the effector domain of G alpha16. Investigations on blood samples from lymphoma patients undergoing salvage therapy with different cytokine support showed that monitoring of the expression of G alpha16 mRNA which appears to play a role in cytokine signalling via tyrosine kinases was a valuable complementation to CD34 screening for analyzing hematopoietic recovery after chemotherapy. We demonstrated that in contrast to CD34 which is only expressed in quiescent cells, G alpha16 transcription occurs independently of cell cycle state. In vitro, we could show that G alpha16 was also a valuable marker for confirming the immature state of ex vivo expanded blood stem cells from patients. A further part of the study was focused on the response of G alpha16 and CD34 expressing cells to the granulocyte-derived hemoregulatory peptide (pyroGlu-Glu-Asp-Cys-Lys)2 = (pEEDCK)2 which harbors a G alpha16-homologous sequence motif. Results obtained from in vitro assays which involved estimation of colony outgrowth from CD34-positive cells showed that the effect of (pEEDCK)2 on CD34 cells enhanced the effect of IL-3 or SCF. These data indicate that G alpha16 may co-operate with (pEEDCK)2 in triggering the cytokine response of immature hematopoietic cells.
Find related publications in this database (using NLM MeSH Indexing)
Antigens, CD34 - biosynthesis Antigens, CD34 - genetics
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Cells, Cultured -
Cytokines - pharmacology
Dimerization -
Drug Synergism -
GTP-Binding Protein alpha Subunits, Gq-G11 -
GTP-Binding Proteins - biosynthesis GTP-Binding Proteins - genetics
Granulocyte Colony-Stimulating Factor - pharmacology
Hematopoiesis - drug effects
Hematopoietic Stem Cells - drug effects Hematopoietic Stem Cells - metabolism
Heterotrimeric GTP-Binding Proteins -
Humans -
Interleukin-11 - pharmacology
Interleukin-3 - pharmacology
Interleukin-6 - pharmacology
Lymphoma - drug therapy Lymphoma - pathology
Neoplasm Proteins - biosynthesis Neoplasm Proteins - genetics
Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism
Oligopeptides - chemistry Oligopeptides - pharmacology
Pyrrolidonecarboxylic Acid - analogs and derivatives
RNA, Messenger - biosynthesis RNA, Messenger - genetics
Salvage Therapy -
Stem Cell Factor - pharmacology
Structure-Activity Relationship -
Transcription, Genetic -
Tumor Cells, Cultured -

Find related publications in this database (Keywords)
hematopoiesis
stem cells
G alpha 16
(pEEDCK)2
cytokines
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