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Differential regulation of SOCS genes in normal and transformed erythroid cells


Sarna, MK; Ingley, E; Busfield, SJ; Cull, VS; Lepere, W; McCarthy, DJ; Wright, MJ; Palmer, GA; Chappell, D; Sayer, MS; Alexander, WS; Hilton, DJ; Starr, R; Watowich, SS; Bittorf, T; Klinken, SP; Tilbrook, PA
2003-05-22
ONCOGENE
Journal Article
22
21
3221-3230
The SOCS family of genes are negative regulators of cytokine signalling with SOCS-1 displaying tumor suppressor activity. SOCS-1, CIS and SOCS-3 have been implicated in the regulation of red blood cell production. In this study, a detailed examination was conducted on the expression patterns of these three SOCS family members in normal erythroid progenitors and a panel of erythroleukemic cell lines. Unexpectedly, differences in SOCS gene expression were observed during maturation of normal red cell progenitors, viz changes to CIS were inversely related to the alterations of SOCS-1 and SOCS-3. Similarly, these SOCS genes were differentially expressed in transformed erythoid cells erythroleukemic cells immortalized at an immature stage of differentiation expressed SOCS-1 and SOCS-3 mRNA constitutively, whereas in more mature cell lines SOCS-1 and CIS were induced only after exposure to erythropoietin (Epo). Significantly, when ectopic expression of the tyrosine kinase Lyn was used to promote differentiation of immature cell lines, constitutive expression of SOCS-1 and SOCS-3 was completely suppressed. Modulation of intracellular signalling via mutated Epo receptors in mature erythroleukemic lines also highlighted different responses by the three SOCS family members. Close scrutiny of SOCS-1 revealed that, despite large increases in mRNA levels, the activity of the promoter did not alter after erythropoietin stimulation; in addition, erythroid cells from SOCS-1-/- mice displayed increased sensitivity to Epo. These observations indicate complex, stage-specific regulation of SOCS genes during normal erythroid maturation and in erythroleukemic cells.
NATURE PUBLISHING GROUP
PHENYLHYDRAZINE-TREATED MICE; PROTEIN-TYROSINE KINASE; ERYTHROPOIETIN RECEPTOR; C-KIT; SIGNAL-TRANSDUCTION; PROGENITOR CELLS; IN-VIVO; ERYTHROLEUKEMIA DEVELOPMENT; TRANSLATIONAL REPRESSION; TRANSCRIPTION FACTOR
10.1038/sj.onc.1206381
Refer to copyright notice on published article.

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Creation Date 2003-05-22 12:00:00