Subdomain 2, Not the Transmembrane Domain, Determines the Dimerization Partner of Growth Hormone Receptor and Prolactin Receptor

• DOI: 10.1210/en.2017-00469
• Publication Date: 2017-08-02T18:07:09Z
• Authors: Ying Liu; Jing Jiang; Bradford Lepik; Yue Zhang; Kurt R Zinn; Stuart J Frank
• Keywords: Prolactin receptor; Cytokine receptor

Growth hormone receptor (GHR) and prolactin (PRL) (PRLR) are homologous transmembrane class I cytokine receptors. In humans, GH interacts with GHR homodimers or PRLR PRL only to promote signaling. human breast cancer cells endogenously expressing both receptors, specifically coimmunoprecipitate. We previously devised a split luciferase complementation assay study assemblages. this technique, firefly is into two fragments (N- C-terminal of the luciferase), each without enzyme activity tethered tails The restore when brought close other by Real-time ligand-induced changes reflect arrangement receptors indicate that GHR/PRLR arranged as heteromultimer comprised GHR-GHR PRLR-PRLR homodimers. now dissect determinants for homodimerization versus heteroassociation. have extracellular domains ligand-binding N-terminal subdomain 1 membrane-proximal 2 (S2), which fosters receptor–receptor contact. Based on previous studies S2 domain (TMD) in dimerization, we constructed GHR(PRLRS2), GHR(PRLRS2-TMD), GHR(PRLRTMD), replacing GHR's alone, plus TMD, TMD alone PRLR's counterpart. tested ability these chimeras homodimerize heteroassociate. Comparing various combinations, found GHR(PRLRS2) GHR(PRLRS2-TMD) behaved PRLR, whereas GHR(PRLRTMD) regarding their dimerization partners. conclude rather than TMDs, determines partner.