The role of microtubule-associated protein 1S in SOCS3 regulation of IL-6 signaling.
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.
Zou
Tingting
T
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
Ouyang
Lu
L
Chen
Lu
L
Dong
Wei
W
Qiao
Hong
H
Liu
Yingle
Y
Qi
Yipeng
Y
D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D015850:Interleukin-6; C493240:MAP1S protein, human; D008869:Microtubule-Associated Proteins; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins