GP130 is the founding member of the tall cytokine receptors and serves as a signal transducing subunit for several cytokines including IL-6, IL-11, IL-27, LIFR, and others. The GP130 family of cytokines are diverse with key roles in immune responses, neural growth, maintenance of stem cell pluripotency and cardiovascular system through signalling via IL-6, CNTF, LIF, and CT-1 [1]. In addition, GP130 has important roles in cancer and inflammation biology as illustrated in mouse models harbouring mutations in the suppressors of cytokine signalling (SOCS) binding region of GP130 resulting in hyper-active signal transducers and activators of transcription (STAT)1 and 3 signalling promoting gastric cancer incidences. Moreover, small in-frame deletions in domain 2 of GP130 have been identified in 60% of patients with inflammatory hepatocellular adenomas (IHCA) making GP130 D2 mutants hepatic oncogenes [2]. Using the dimerisation domain of the c-jun transcription factors, we have generated GP130 monomers clamped together on the cell surface of the pro-B cell line, Ba/F3. The effect of length, charge, and rotation of the GP130 extracellular juxtamembrane region was investigated resulting in identification of active and inactive receptor models. Variable rotations of the GP130 transmembrane and intracellular domains induced by alanine insertions led to differential activation of JAK/STAT and MAPK signalling pathways and generated distinct proliferative responses in Ba/F3 cells. These models with FRET reporters fused after the JAK binding Box1-2 region were generated to determine movements of the intracellular domains of GP130 with their associated JAK kinases. This study will allow deciphering the mechanism of activation of GP130 and its JAK partners and will help in designing drugs targeting deleterious effects of IL-6 or IL-11.