The role of microtubule-associated protein 1S in SOCS3 regulation of IL-6 signaling

Abstract 

Cytokine-induced suppressor of cytokine signaling (SOCS) proteins function as feedback inhibitors of cytokine receptor signaling by inhibiting the Janus kinase–signal transducer and activator of transcription (JAK–STAT) signal transduction pathway. In this report, microtubule-associated protein 1S (MAP1), a member of the MAP1 family, was identified as a novel SOCS3 interacting protein. MAP1S could bind with microtubules and actin, and decorated and stabilized microtubules. A perinuclear co-localization was discovered between MAP1S and SOCS3. In MAP1S deficient macrophages, inhibition of SOCS3 on STAT3 phosphorylation can be partially hindered in the presence of interleukin-6 (IL-6) and lipopolysaccharide (LPS). The microtubule-depolymerizing drug nocodazole also disrupted the inhibitory activity of the SOCS3 protein. These results suggest that the interaction of SOCS3 with MAP1S and the integrity of the microtubule cytoskeleton play an important role in the negative regulation of SOCS3 on IL-6 signaling.

Structured summary

Abbreviations: SOCS, suppressor of cytokine signaling, MAP1, microtubule-associated protein 1, LPS, lipopolysaccharide, IL-6, interleukin-6, JAK, Janus kinase, STAT, signal transducer and activator of transcription, CIS, cytokine-inducible Src homology 2-containing protein, KIR, kinase inhibitory region, TLR, toll like receptor, MTOC, microtubule organizing center, RASSF1A, Ras association domain family 1, isoform A, VCY2, variably charged protein Y2, APRE, acute-phase response element, IRS-1, insulin receptor substrate 1, GHR, growth hormone receptor, GST, glutathione S-transferase

Keywords: SOCS3, MAP1S, Microtubule cytoskeleton, IL-6, Negative regulation