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A region encompassing the FERM domain of Jak1 is necessary for binding to the cytokine receptor gp130
Author(s) -
Hilkens Catharien M.U.,
Is'harc Hayaatun,
Lillemeier Björn F.,
Strobl Birgit,
Bates Paul A.,
Behrmann Iris,
Kerr Ian M.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02783-1
Subject(s) - glycoprotein 130 , cytokine receptor , ferm domain , janus kinase , tyrosine kinase 2 , janus kinase 1 , receptor , microbiology and biotechnology , biology , chemistry , biochemistry , signal transduction , stat3 , membrane protein , integral membrane protein , platelet derived growth factor receptor , membrane , growth factor
The terminal portion of the Janus kinases (Jaks) contains a divergent FERM ( our‐point‐one, zrin, adixin, oesin) homology domain comprising 19 conserved hydrophobic regions. 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 investigated. Chimeras 1, 2 and 3 (Jak1 FERM regions 1–19, 1–18 and 1–8/Jak3, respectively) were all enzymically active. Chimeras 1 and 2 interacted with the cytoplasmic domain of gp130, although less efficiently than Jak1. Only chimera 2, however, restored gp130 signalling in Jak1‐negative cells. The data are consistent with recruitment of Jak1 to gp130 through the Jak1 FERM domain, but also emphasise the likely requirement for precise Jak/receptor orientation to sustain function.