Suppressor of Cytokine Signaling 3 Controls Lysosomal Routing of G-CSF Receptor

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2007 Mar 17

PMID 17363902

Citations 45

Authors

Mahban I Irandoust

Lambertus H J Aarts

Onno Roovers

Judith Gits

Stefan J Erkeland

Ivo P Touw

Affiliations

Soon will be listed here.

Abstract

The hematopoietic system provides an attractive model for studying growth factor-controlled expansion and differentiation of cells in relation to receptor routing and its consequences for signal transduction. Suppressor of cytokine signaling (SOCS) proteins regulate receptor signaling partly via their ubiquitin ligase (E3)-recruiting SOCS box domain. Whether SOCS proteins affect signaling through modulating intracellular trafficking of receptors is unknown. Here, we show that a juxtamembrane lysine residue (K632) of the granulocyte colony-stimulating factor receptor (G-CSFR) plays a key role in receptor routing and demonstrate that the effects of SOCS3 on G-CSF signaling to a major extent depend on this lysine. Mutation of K632 causes accumulation of G-CSFR in early endosomes and leads to sustained activation of signal transducer and activator of transcription 5 and ERK, but not protein kinase B. Myeloid progenitors expressing G-CSFR mutants lacking K632 show a perturbed proliferation/differentiation balance in response to G-CSF. This is the first demonstration of SOCS-mediated ubiquitination and routing of a cytokine receptor and its impact on maintaining an appropriate signaling output.

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References

de Koning J, Schelen A, Smith L, van Leeuwen D, Santini V, Burgering B . Proliferation signaling and activation of Shc, p21Ras, and Myc via tyrosine 764 of human granulocyte colony-stimulating factor receptor. Blood. 1998; 91(6):1924-33. View

Ward A, Hermans M, Smith L, van Aesch Y, Schelen A, Antonissen C . Tyrosine-dependent and -independent mechanisms of STAT3 activation by the human granulocyte colony-stimulating factor (G-CSF) receptor are differentially utilized depending on G-CSF concentration. Blood. 1998; 93(1):113-24. View

Govers R, ten Broeke T, van Kerkhof P, Schwartz A, Strous G . Identification of a novel ubiquitin conjugation motif, required for ligand-induced internalization of the growth hormone receptor. EMBO J. 1999; 18(1):28-36. PMC: 1171099. DOI: 10.1093/emboj/18.1.28. View

Hunter M, Avalos B . Deletion of a critical internalization domain in the G-CSFR in acute myelogenous leukemia preceded by severe congenital neutropenia. Blood. 1999; 93(2):440-6. View

Ward A, van Aesch Y, Schelen A, Touw I . Defective internalization and sustained activation of truncated granulocyte colony-stimulating factor receptor found in severe congenital neutropenia/acute myeloid leukemia. Blood. 1999; 93(2):447-58. View

Ward A, Smith L, de Koning J, van Aesch Y, Touw I . Multiple signals mediate proliferation, differentiation, and survival from the granulocyte colony-stimulating factor receptor in myeloid 32D cells. J Biol Chem. 1999; 274(21):14956-62. DOI: 10.1074/jbc.274.21.14956. View

Uotani S, Bjorbaek C, Tornoe J, Flier J . Functional properties of leptin receptor isoforms: internalization and degradation of leptin and ligand-induced receptor downregulation. Diabetes. 1999; 48(2):279-86. DOI: 10.2337/diabetes.48.2.279. View

Harada M, Qin Y, Takano H, Minamino T, Zou Y, Toko H . G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med. 2005; 11(3):305-11. DOI: 10.1038/nm1199. View

Dunn S, Bjornholm M, Bates S, Chen Z, Seifert M, Myers Jr M . Feedback inhibition of leptin receptor/Jak2 signaling via Tyr1138 of the leptin receptor and suppressor of cytokine signaling 3. Mol Endocrinol. 2004; 19(4):925-38. DOI: 10.1210/me.2004-0353. View

10.

Royer Y, Staerk J, Costuleanu M, Courtoy P, Constantinescu S . Janus kinases affect thrombopoietin receptor cell surface localization and stability. J Biol Chem. 2005; 280(29):27251-61. DOI: 10.1074/jbc.M501376200. View

11.

Del Pozo M, Balasubramanian N, Alderson N, Kiosses W, Grande-Garcia A, Anderson R . Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nat Cell Biol. 2005; 7(9):901-8. PMC: 1351395. DOI: 10.1038/ncb1293. View

12.

Lu J, Piazza T, Schuler L . Proteasomes mediate prolactin-induced receptor down-regulation and fragment generation in breast cancer cells. J Biol Chem. 2005; 280(40):33909-16. PMC: 1976473. DOI: 10.1074/jbc.M508118200. View

13.

Zhuang D, Qiu Y, Haque S, Dong F . Tyrosine 729 of the G-CSF receptor controls the duration of receptor signaling: involvement of SOCS3 and SOCS1. J Leukoc Biol. 2005; 78(4):1008-15. DOI: 10.1189/jlb.0105032. View

14.

Tannahill G, Elliott J, Barry A, Hibbert L, Cacalano N, Johnston J . SOCS2 can enhance interleukin-2 (IL-2) and IL-3 signaling by accelerating SOCS3 degradation. Mol Cell Biol. 2005; 25(20):9115-26. PMC: 1265772. DOI: 10.1128/MCB.25.20.9115-9126.2005. View

15.

Shao H, Xu X, Jing N, Tweardy D . Unique structural determinants for Stat3 recruitment and activation by the granulocyte colony-stimulating factor receptor at phosphotyrosine ligands 704 and 744. J Immunol. 2006; 176(5):2933-41. DOI: 10.4049/jimmunol.176.5.2933. View

16.

Belouzard S, Rouille Y . Ubiquitylation of leptin receptor OB-Ra regulates its clathrin-mediated endocytosis. EMBO J. 2006; 25(5):932-42. PMC: 1409713. DOI: 10.1038/sj.emboj.7600989. View

17.

Polo S, Di Fiore P . Endocytosis conducts the cell signaling orchestra. Cell. 2006; 124(5):897-900. DOI: 10.1016/j.cell.2006.02.025. View

18.

Piessevaux J, Lavens D, Montoye T, Wauman J, Catteeuw D, Vandekerckhove J . Functional cross-modulation between SOCS proteins can stimulate cytokine signaling. J Biol Chem. 2006; 281(44):32953-66. DOI: 10.1074/jbc.M600776200. View

19.

Dong F, Larner A . Activation of Akt kinase by granulocyte colony-stimulating factor (G-CSF): evidence for the role of a tyrosine kinase activity distinct from the Janus kinases. Blood. 2000; 95(5):1656-62. View

20.

de Koning J, Ward A, Schelen A, Antonissen C, van Leeuwen D, Lowenberg B . STAT3-mediated differentiation and survival and of myeloid cells in response to granulocyte colony-stimulating factor: role for the cyclin-dependent kinase inhibitor p27(Kip1). Oncogene. 2000; 19(29):3290-8. DOI: 10.1038/sj.onc.1203627. View