Suppressor of cytokine signaling 3 (SOCS3) modulates the JAK/STAT genes in Korean black rockfish (Sebastes schlegelii)

Cytokines have crucial roles in the immune system by controlling the proliferation and differentiation of the immune cells. Correspondingly, Janus family tyrosine kinases (JAKs) are essential signaling molecules for cytokine signaling. However, members of suppressor of cytokine signaling (SOCS) protein family play an important role to regulation of cytokine signaling via JAK-STAT pathway. SOCS proteins inhibit cytokine signaling systems in a classical negative-feedback loop. SOCS molecules possess a central SH2 domain and a carboxyl terminal domain named the SOCS box. The target of each SOCS and CISH is determined by the SH2 domain which binds to phosphorylated tyrosine residues. Additionally, only SOCS1 and 3 possess a kinase inhibitory region (KIR), which is located at the N-terminus, immediately upstream of the central SH2 domain. Here in, we have characterized the molecular aspects of suppressor of cytokine signaling from black rockfish (RfSOCS3). Series of bioinformatics tools were used to discover the domain architecture of the RfSOCS3 protein. Transcriptional variation of RfSOCS3 was determined under aseptic and septic conditions of rockfish.  In order to analyze the STAT gene regulation effect of RfSOCS3, it was transfect into rockfish testis cells and evaluates the transcriptional variation of different STAT members of rockfish. According to the in silico analysis this protein has a molecular weight of 23 kDa and a theoretical pI value of 9.2. Domain architecture analysis revealed that this protein has a conserved SH2 superfamily domain and SOCS superfamily domain which are vital for the cell signaling transduction process. C-terminal SOCS box and a central SH2 domain are the characteristic features in this SH2 family members. SOCS3 is involved in the down-regulation of the JAK/STAT pathway and it inhibits JAK activity indirectly through recruitment to the cytokine receptors. There is no significant transcriptional modulation observed in RfSOCS3 transfected and pcDNA transfected cells in compared to control cells. However, there is significant up-regulation of RfSTAT genes in poly:IC treated cells compared to the un-treated cells. Later on the RfSTAT-1, -3 and -6 transcripts were down-regulated in RfSOCS3 transfected, poly:IC treated cells revealing the inhibition of RfJAK activity by RfSOCS3. Moreover, ubiquitous expression of RfSOCS3 transcripts was observed in healthy rock fish tissues with different magnitudes with highest expression in blood. Collectively, we can suggest that RfSOCS3 play an important role in the rockfish JAK/STAT pathway and down-regulate the STAT genes via inhibition of JAK activity.