Cytokine signaling pathways

Shuai K. 2006. Regulation of cytokine signaling pathways by PIAs proteins. Cell Res. 16 196-202. 

JAK proteins and at least one of several STAT proteins are Involved in signaling downstream from all cytokine receptors. To understand how JAK and STAT proteins function, we examine one of the best-understood cytokine signaling pathways, that downstream of the erythropoietin receptor. 

Yasukawa, H., A. Sasaki, and A. Yoshimura. 2000. Negative regulation of cytokine signaling pathways. Ann. Rev. Immunol. 18 43-164. 

O Shea, J.J., Gadina, M., and Schreiber, R.D. 2002. Cytokine signalling in 2002 new surprises in the JAK/STAT pathway. Cell 109, S121-S131. 

Fig. 7.3. Osteoclastogenesis after estrogen deficiency. Estrogen deprivation leads to an increase in the synthesis of RANKL for stromal/OB cells of the BM. This increase in the expression of RANKL leads to an increase in OCS. Estrogen deficiency also induces the synthesis and secretion of cytokines, such as IL-6 and M-CSF, that increase the number of preosteoclasts in the BM, and thus increases OCS. Nonetheless, certain cells of the immune system, such as monocytes and T-cells, intervene in the process when the supply of estrogens fails. These cells secrete IL-1 and TNF-a that are powerful inductors of OCS. When estrogens or agonists of estrogen receptors like raloxifene are administered, the synthesis and secretion of many of the mentioned cytokines diminish and the synthesis and liberation of OPG and TGF-/S are stimulated. These molecules inhibit OCS by inhibiting the RANKL/RANK signal pathway and by promoting osteoclast apoptosis...

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