Cytokine-like receptor transcripts

Several signal cytokine receptor-like transcripts are rapidly induced after GATA-1 activation. Both Csf2rb1 and Csf2rb2 transcripts are strongly upregulated within the first three hours, and continue to increase over the remaining time course. Csf2rb2 is the beta-chain common to the IL3, IL5 and GM-CSF receptors, while Csf2rb1 pairs only with IL3 alpha chain. RT-PCR analysis using a unique restriction site demonstrated that both beta chains are induced in G1E cells (not shown). A truncated form of Csf2rb2 was not present in G1E cells, although it was detected in uninduced MEL cells (not shown). The common beta chain was strongly induced in the erythroid differentiation system derived from fetal liver cells 1. Corresponding alpha genes for IL3, IL5 and GM-CSF were deemed "absent" by the chip, but low levels of IL3 alpha chain (Csf2ra1) were detected by PCR (not shown).

This discrepancy in IL3 alpha and beta chains has been previously reported 2, and may indicate a role for the beta chain in conjunction with other partners. While the beta chain may play an accessory role in erythropoietin receptor (EpoR ) (reviewed in 2) or Kit signaling, this role is not vital as hematopoietic cells from mouse cells null for both beta chains had normal responses to EpoR and stem cell factor 3. An unrecognized alpha-like partner may be present in differentiating erythroblasts.

The uncharacterized cytokine-receptor-like molecules, Crlf1 and Crlf3 (crème-9) were strongly induced within the first three hours (see list of most-modulated transcripts for 3, 7 and 14 hours). These proteins resemble hematopoietic family cytokine receptors. Both contain WSXWS motif and a fibronectin III domain, but Crlf3 it lacks conserved cysteines expected in a cytokine binding domain. Their similarity to cytokine receptors may allow them to interact with tyrosine kinases or modulators of tyrosine kinase signaling.

An EST (Riken 0610011C19) was rapidly and consistently induced, and the pattern verified by Northern blotting. BLAST analysis demonstrated correspondence to LZP, a small protein possessing a minimal leucine zinc-finger region. LZP was previously identified in a screen for stromal proteins promoting cell proliferation. Transfection of LZP into stromal cells promoted in vitro propagation of co-cultured bone marrow cells and splenocytes 4. LZP production by red cells may regulate their own growth or influence the marrow microenvironment.

References

1. Dolznig H, Boulme F, Stangl K, Deiner EM, Mikulits W, Beug H, Mullner EW. Establishment of normal, terminally differentiating mouse erythroid progenitors: molecular characterization by cDNA arrays. Faseb J. 2001;15:1442-1444
2. Carta C, Campisi S, Migliaccio G, Migliaccio A. Erythropoietin-dependent suppression of the expression of the beta subunits of the interleukin-3 receptor during erythroid differentiation. Blood Cells, Molecules and Diseases. 2000;26:467-478
3. Scott C, Robb L, Papaevangeliou B, Mansfield R, Nicola N, Begley C. Reassessment of interactions between hematopoietic receptors using common beta-chain and interleukin-3-specific receptor beta-chain-null cells: no evidence of functional interactions with receptors for erythropoietin, granulocyte colony-stimulating factor, or stem cell factor. Blood. 2000;96:1588-1590
4. Tulin EE, Onada N, Hasegawa M, Nosaka T, Nomura H, Kitamura T. Genetic approach and phenotype-based complementation screening for identification of stroma cell-derived proteins involved in cell proliferation. Exp Cell Res. 2002;272:23-32
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Please direct all comments to: John Welch, M.D., Ph.D.
Last modification: May 21, 2004