A New Mechanism for Growth Hormone Receptor Activation of JAK2, and Implications for Related Cytokine Receptors

Overview

Journal JAKSTAT

Date 2014 Aug 8

PMID 25101218

Citations 13

Authors

Michael J Waters

Andrew J Brooks

Yash Chhabra

Affiliations

Soon will be listed here.

Abstract

The growth hormone receptor was the first cytokine receptor to be cloned and crystallized, and provides a valuable exemplar for activation of its cognate kinase, JAK2. We review progress in understanding its activation mechanism, in particular the molecular movements made by this constitutively dimerized receptor in response to ligand binding, and how these lead to a separation of JAK-binding Box1 motifs. Such a separation leads to removal of the pseudokinase inhibitory domain from the kinase domain of a partner JAK2 bound to the receptor, and vice versa, leading to apposition of the kinase domains and transactivation. This may be a general mechanism for class I cytokine receptor action.

Citing Articles

Molecular and cellular factors determining the functional pleiotropy of cytokines.

McFarlane A, Pohler E, Moraga I FEBS J. 2022; 290(10):2525-2552.

PMID: 35246947 PMC: 10952290. DOI: 10.1111/febs.16420.

Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET.

Lay C, Bridges A, Goulding J, Briddon S, Soloviev Z, Craggs P Cell Chem Biol. 2021; 29(1):19-29.e6.

PMID: 34038748 PMC: 8790524. DOI: 10.1016/j.chembiol.2021.05.002.

Short stature explained by dimerization of human growth hormone induced by a p.C53S point mutation.

Sander M, Wu Z, Strasburger C J Biol Chem. 2020; 295(15):4893-4901.

PMID: 32132170 PMC: 7152745. DOI: 10.1074/jbc.RA119.009101.

Mapping Determinants of Cytokine Signaling via Protein Engineering.

Gorby C, Martinez-Fabregas J, Wilmes S, Moraga I Front Immunol. 2018; 9:2143.

PMID: 30319612 PMC: 6170656. DOI: 10.3389/fimmu.2018.02143.

EPO does not promote interaction between the erythropoietin and beta-common receptors.

Cheung Tung Shing K, Broughton S, Nero T, Gillinder K, Ilsley M, Ramshaw H Sci Rep. 2018; 8(1):12457.

PMID: 30127368 PMC: 6102255. DOI: 10.1038/s41598-018-29865-x.

References

Fuh G, Cunningham B, Fukunaga R, Nagata S, Goeddel D, Wells J . Rational design of potent antagonists to the human growth hormone receptor. Science. 1992; 256(5064):1677-80. DOI: 10.1126/science.256.5064.1677. View

Brown R, Adams J, Pelekanos R, Wan Y, McKinstry W, Palethorpe K . Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol. 2005; 12(9):814-21. DOI: 10.1038/nsmb977. View

Argetsinger L, Campbell G, Yang X, Witthuhn B, Silvennoinen O, Ihle J . Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell. 1993; 74(2):237-44. DOI: 10.1016/0092-8674(93)90415-m. View

Wan Y, Zheng Y, Harris J, Brown R, Waters M . Epitope map for a growth hormone receptor agonist monoclonal antibody, MAb 263. Mol Endocrinol. 2003; 17(11):2240-50. DOI: 10.1210/me.2003-0162. View

Bernat B, Pal G, Sun M, Kossiakoff A . Determination of the energetics governing the regulatory step in growth hormone-induced receptor homodimerization. Proc Natl Acad Sci U S A. 2003; 100(3):952-7. PMC: 298707. DOI: 10.1073/pnas.0235023100. View

Kubatzky K, Ruan W, Gurezka R, Cohen J, Ketteler R, Watowich S . Self assembly of the transmembrane domain promotes signal transduction through the erythropoietin receptor. Curr Biol. 2001; 11(2):110-5. DOI: 10.1016/s0960-9822(01)00018-5. View

Wilks A, Harpur A, Kurban R, Ralph S, Zurcher G, Ziemiecki A . Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Mol Cell Biol. 1991; 11(4):2057-65. PMC: 359893. DOI: 10.1128/mcb.11.4.2057-2065.1991. View

Staerk J, Lacout C, Sato T, Smith S, Vainchenker W, Constantinescu S . An amphipathic motif at the transmembrane-cytoplasmic junction prevents autonomous activation of the thrombopoietin receptor. Blood. 2005; 107(5):1864-71. PMC: 1379661. DOI: 10.1182/blood-2005-06-2600. View

Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen O . The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol. 2011; 18(9):971-6. PMC: 4504201. DOI: 10.1038/nsmb.2099. View

10.

Yang N, Langenheim J, Wang X, Jiang J, Chen W, Frank S . Activation of growth hormone receptors by growth hormone and growth hormone antagonist dimers: insights into receptor triggering. Mol Endocrinol. 2007; 22(4):978-88. PMC: 2276467. DOI: 10.1210/me.2007-0424. View

11.

Jiang J, Wan Y, Wang X, Xu J, Harris J, Lobie P . Inhibitory GH receptor extracellular domain monoclonal antibodies: three-dimensional epitope mapping. Endocrinology. 2011; 152(12):4777-88. PMC: 3230063. DOI: 10.1210/en.2011-1336. View

12.

Liongue C, Ward A . Evolution of Class I cytokine receptors. BMC Evol Biol. 2007; 7:120. PMC: 1963337. DOI: 10.1186/1471-2148-7-120. View

13.

Poger D, Mark A . Turning the growth hormone receptor on: evidence that hormone binding induces subunit rotation. Proteins. 2009; 78(5):1163-74. DOI: 10.1002/prot.22636. View

14.

Qazi A, Tsai-Morris C, Dufau M . Ligand-independent homo- and heterodimerization of human prolactin receptor variants: inhibitory action of the short forms by heterodimerization. Mol Endocrinol. 2006; 20(8):1912-23. DOI: 10.1210/me.2005-0291. View

15.

Behncken S, Billestrup N, Brown R, Amstrup J, Waters M . Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation. J Biol Chem. 2000; 275(22):17000-7. DOI: 10.1074/jbc.275.22.17000. View

16.

Matthews E, Thevenin D, Rogers J, Gotow L, Lira P, Reiter L . Thrombopoietin receptor activation: transmembrane helix dimerization, rotation, and allosteric modulation. FASEB J. 2011; 25(7):2234-44. PMC: 3114528. DOI: 10.1096/fj.10-178673. View

17.

Waters M, Brooks A . Growth hormone receptor: structure function relationships. Horm Res Paediatr. 2011; 76 Suppl 1:12-6. DOI: 10.1159/000329138. View

18.

Clackson T, Ultsch M, Wells J, de Vos A . Structural and functional analysis of the 1:1 growth hormone:receptor complex reveals the molecular basis for receptor affinity. J Mol Biol. 1998; 277(5):1111-28. DOI: 10.1006/jmbi.1998.1669. View

19.

Gadd S, Clevenger C . Ligand-independent dimerization of the human prolactin receptor isoforms: functional implications. Mol Endocrinol. 2006; 20(11):2734-46. DOI: 10.1210/me.2006-0114. View

20.

Brooks A, Dai W, OMara M, Abankwa D, Chhabra Y, Pelekanos R . Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science. 2014; 344(6185):1249783. DOI: 10.1126/science.1249783. View