Here's a recent review by Ihle (another Ligand consultant) that specifically mentions EPO:
Stem Cells 1997;15 Suppl 1:105-111
Jaks and Stats in cytokine signaling.
Ihle JN, Nosaka T, Thierfelder W, Quelle FW, Shimoda K
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Hematopoiesis is regulated through the binding of cytokines to receptors of the cytokine receptor superfamily. Although lacking
catalytic domains, members of the cytokine receptor superfamily mediate ligand-dependent activation of protein tyrosine
phosphorylation through their association and activation of members of the Janus kinase (Jak) family of protein tyrosine
kinases. The activated Jaks phosphorylate the receptors which creates docking sites for SH2-containing signaling proteins
which are tyrosine phosphorylated following their association with the complex. Among the substrates of tyrosine
phosphorylation are members of the signal transducers and activators of the transcription family of proteins (Stats). Various
cytokines induce the tyrosine phosphorylation and activation of one or more of the seven family members. The pattern of Stat
activation provides a level of cytokine individuality that is not observed in the activation of other signaling pathways. The role of
various Stats in the biological responses to cytokines has been assessed through the analysis of receptor mutations which
disrupt Stat activation and more recently by disruption of the genes in mice. Our results have demonstrated that the activation
of Stat5a and Stat5b by erythropoietin is critical for the activation of a number of immediate early genes but is not required for
a mitogenic response. Mice in which the genes for Stat4 and Stat6 are disrupted are viable but lack functions that are mediated
by interleukin 12 (IL-12) or IL-4, respectively, suggesting that these Stats perform very specific functions in immune responses.
Publication Types:
Review
Review, tutorial
PMID: 9368330, UI: 98034700 |
