A region encompassing the FERM domain of Jak1 is necessary for binding to the cytokine receptor gp130

The terminal portion of the Janus kinases (Jaks) contains a divergent FERM ((F) under bar our-point-one, (E) under bar zrin, (R) under bar adixin, (M) under bar oesin) homology domain comprising 19 conserved hydrophobic regio ns. To determine the role of this domain in governing recruitment of Jak1, but not Jak3, to the gp130 subunit of the interleukin-6 family of cytokine receptors, the interaction of three Jak1/Jak3 chimeras with gp130 was inves tigated. Chimeras 1, 2 and 3 (Jak1 FERM regions 1-19, 1-18 and 1-8/Jak3, re spectively) were all enzymically active. Chimeras 1 and 2 interacted with t he cytoplasmic domain of gp130, although less efficiently than Jak1. Only c himera 2, however, restored gp130 signalling in Jak1-negative cells. The da ta are consistent with recruitment of Jak1 to gp130 through the Jak1 FERM d omain , but also emphasise the likely requirement for precise Jak1 receptor orientation to sustain function. (C) 2001 Federation of European Biochemic al Societies. Published by Elsevier Science B.V. All rights reserved.