Regulation of Cytokine Signaling Pathways in the Eye

Egwuagu, Charles

Abstract

Suppressors of cytokine signaling (SOCS) are a family of inducible feed-back regulators of cytokines that signal through tyrosine kinases and the JAK/STAT signaling pathway. Thus far 6 distinct members have been described and depending on the tissue, different SOCS are activated in response to particular cytokines or growth factors. Several cytokines (PDGF, EGF, IGF) implicated in lens growth and differentiation activate JAK kinases and STAT pathways. However, regulatory mechanisms that switch-off signals transmitted by these cytokines are unknown. We determined by Western blotting and RT-PCR analyses whether SOCS and STAT genes are constitutively and inducibly expressed in rat and mouse lenses, as well as, some well characterized lens epithelial cell lines. Cultured lens cells were also treated with either PDGF, EGF or IGF to characterize the repertoire of SOCS genes induced in lens cells by these growth factors. Authenticity of the SOCS transcripts was verified by DNA sequence analysis. Expression of all known STATs, with exception STAT2 and STAT4 was detected. Constitutive expression of most SOCS members (except SOCS1) was also detected in the murine lens and lens cell lines. Our data suggest that SOCS proteins may play significant roles in switching-off JAK/STAT signals in the ocular lens. Further characterization of lens SOCS proteins may provide valuable insight into the role of these negative regulators of cytokine signaling in lens and eye development.