| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 274, Issue 50, 35553-35561, December 10, 1999
From the Department of Biology, Division of Cell and Molecular
Biology, Boston University, Boston, Massachusetts 02215
The inhibition of growth hormone (GH) signaling
by five members of the GH-inducible suppressor of cytokine signaling
(SOCS/CIS) family was investigated in transfected COS cells. Complete
inhibition of GH activation of the signal transducer STAT5b and
STAT5b-dependent transcriptional activity was observed upon
expression of SOCS-1 or SOCS-3, while partial inhibition (CIS, SOCS-2)
or no inhibition (SOCS-6) was seen with other SOCS/CIS family members.
SOCS-1, SOCS-2, SOCS-3, and CIS each strongly inhibited the GH receptor (GHR)-dependent tyrosine phosphorylation of JAK2 seen at
low levels of transfected JAK2; however, only SOCS-1 strongly inhibited
the GHR-independent tyrosine phosphorylation of JAK2 seen at higher JAK2 levels. To probe for interactions with GHR, in vitro
binding assays were carried out using glutathione
S-transferase-GHR fusion proteins containing variable
lengths of GHR's COOH-terminal cytoplasmic domain. CIS and SOCS-2
bound to fusions containing as few as 80 COOH-terminal GHR residues,
provided the fusion protein was tyrosine-phosphorylated. By contrast,
SOCS-3 binding required tyrosine-phosphorylated GHR membrane-proximal
sequences, SOCS-1 binding was tyrosine phosphorylation-independent, and
SOCS-6 did not bind the GHR fusion proteins at all. Mutation of GHR's
membrane-proximal tyrosine residues 333 and 338 to phenylalanine suppressed the inhibition by SOCS-3, but not by CIS, of GH signaling to
STAT5b. SOCS/CIS proteins can thus inhibit GH signaling to STAT5b by
three distinct mechanisms, distinguished by their molecular targets
within the GHR-JAK2 signaling complex, as exemplified by SOCS-1 (direct
JAK2 kinase inhibition), SOCS-3 (inhibition of JAK2 signaling via
membrane-proximal GHR tyrosines 333 and 338), and CIS and SOCS-2
(inhibition via membrane-distal tyrosine(s)).
SOCS/CIS Protein Inhibition of Growth Hormone-stimulated STAT5
Signaling by Multiple Mechanisms*
*
This work was supported in part by National Institutes of
Health Grant DK33765 (to D. J. W.)The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Biology, 5 Cummington St., Boston, MA 02215. Fax: 617-353-7404;
E-mail: djw@bio.bu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Piessevaux, L. De Ceuninck, D. Catteeuw, F. Peelman, and J. Tavernier Elongin B/C Recruitment Regulates Substrate Binding by CIS J. Biol. Chem., August 1, 2008; 283(31): 21334 - 21346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hosui and L. Hennighausen Genomic dissection of the cytokine-controlled STAT5 signaling network in liver Physiol Genomics, July 9, 2008; 34(2): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kenth, J. A M. Mergelas, and C. G. Goodyer Developmental changes in the human GH receptor and its signal transduction pathways J. Endocrinol., July 1, 2008; 198(1): 71 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nielsen, L. C. Gormsen, N. Jessen, S. B. Pedersen, N. Moller, S. Lund, and J. O. L. Jorgensen Growth Hormone Signaling in Vivo in Human Muscle and Adipose Tissue: Impact of Insulin, Substrate Background, and Growth Hormone Receptor Blockade J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2842 - 2850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Tan and M. T Nevalainen Signal transducer and activator of transcription 5A/B in prostate and breast cancers Endocr. Relat. Cancer, June 1, 2008; 15(2): 367 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Uyttendaele, I. Lemmens, A. Verhee, A.-S. De Smet, J. Vandekerckhove, D. Lavens, F. Peelman, and J. Tavernier Mammalian Protein-Protein Interaction Trap (MAPPIT) Analysis of STAT5, CIS, and SOCS2 Interactions with the Growth Hormone Receptor Mol. Endocrinol., November 1, 2007; 21(11): 2821 - 2831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Barclay, S. T. Anderson, M. J. Waters, and J. D. Curlewis Regulation of Suppressor of Cytokine Signaling 3 (SOC3) by Growth Hormone in Pro-B Cells Mol. Endocrinol., October 1, 2007; 21(10): 2503 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Barclay, S. T. Anderson, M. J. Waters, and J. D. Curlewis Characterization of the SOCS3 Promoter Response to Prostaglandin E2 in T47D Cells Mol. Endocrinol., October 1, 2007; 21(10): 2516 - 2528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Deng, K. He, X. Wang, N. Yang, C. Thangavel, J. Jiang, S. Y. Fuchs, and S. J. Frank Determinants of Growth Hormone Receptor Down-Regulation Mol. Endocrinol., July 1, 2007; 21(7): 1537 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. V. Laz, M. G. Holloway, C.-S. Chen, and D. J. Waxman Characterization of Three Growth Hormone-Responsive Transcription Factors Preferentially Expressed in Adult Female Liver Endocrinology, July 1, 2007; 148(7): 3327 - 3337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Ahmed, M. D. Buzzelli, C. H. Lang, J. B. Capen, M. L. Shumate, M. Navaratnarajah, M. Nagarajan, and R. N. Cooney Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1793 - G1803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M A Hyatt, G S Gopalakrishnan, J Bispham, S Gentili, I C McMillen, S M Rhind, M T Rae, C E Kyle, A N Brooks, C Jones, et al. Maternal nutrient restriction in early pregnancy programs hepatic mRNA expression of growth-related genes and liver size in adult male sheep J. Endocrinol., January 1, 2007; 192(1): 87 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Sukiennicki and D. J. Fowell Distinct Molecular Program Imposed on CD4+ T Cell Targets by CD4+CD25+ Regulatory T Cells J. Immunol., November 15, 2006; 177(10): 6952 - 6961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Piessevaux, D. Lavens, T. Montoye, J. Wauman, D. Catteeuw, J. Vandekerckhove, D. Belsham, F. Peelman, and J. Tavernier Functional Cross-modulation between SOCS Proteins Can Stimulate Cytokine Signaling J. Biol. Chem., November 3, 2006; 281(44): 32953 - 32966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. L. Jorgensen, N. Jessen, S. B. Pedersen, E. Vestergaard, L. Gormsen, S. A. Lund, and N. Billestrup GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E899 - E905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhu, M. S. Chang, R. C. Hsueh, R. Taussig, K. D. Smith, M. I. Simon, and S. Choi Dual Ligand Stimulation of RAW 264.7 Cells Uncovers Feedback Mechanisms That Regulate TLR-Mediated Gene Expression J. Immunol., October 1, 2006; 177(7): 4299 - 4310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Anderson, P. Beijer, A. S. Bang, M. A. Fenwick, S. J. Bunn, and D. R. Grattan Suppression of Prolactin-Induced Signal Transducer and Activator of Transcription 5b Signaling and Induction of Suppressors of Cytokine Signaling Messenger Ribonucleic Acid in the Hypothalamic Arcuate Nucleus of the Rat during Late Pregnancy and Lactation Endocrinology, October 1, 2006; 147(10): 4996 - 5005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu, Z. Liu, T. L. Clemens, and J. L. Messina Insulin Reverses Growth Hormone-induced Homologous Desensitization J. Biol. Chem., August 4, 2006; 281(31): 21594 - 21606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lavens, T. Montoye, J. Piessevaux, L. Zabeau, J. Vandekerckhove, K. Gevaert, W. Becker, S. Eyckerman, and J. Tavernier A complex interaction pattern of CIS and SOCS2 with the leptin receptor J. Cell Sci., June 1, 2006; 119(11): 2214 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Bullock, J. E. Debreczeni, A. M. Edwards, M. Sundstrom, and S. Knapp Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase PNAS, May 16, 2006; 103(20): 7637 - 7642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Staub and D. Rotin Role of Ubiquitylation in Cellular Membrane Transport Physiol Rev, April 1, 2006; 86(2): 669 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Flores-Morales, C. J. Greenhalgh, G. Norstedt, and E. Rico-Bautista Negative Regulation of Growth Hormone Receptor Signaling Mol. Endocrinol., February 1, 2006; 20(2): 241 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Landsman and D. J. Waxman Role of the Cytokine-induced SH2 Domain-containing Protein CIS in Growth Hormone Receptor Internalization J. Biol. Chem., November 11, 2005; 280(45): 37471 - 37480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. He, K. Loesch, J. W. Cowan, X. Li, L. Deng, X. Wang, J. Jiang, and S. J. Frank Janus Kinase 2 Enhances the Stability of the Mature Growth Hormone Receptor Endocrinology, November 1, 2005; 146(11): 4755 - 4765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Lindberg, S G Ronn, D Tornehave, H Richter, J A Hansen, J Romer, M Jackerott, and N Billestrup Regulation of pancreatic {beta}-cell mass and proliferation by SOCS-3 J. Mol. Endocrinol., October 1, 2005; 35(2): 231 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Shumate, G. Yumet, T. A. Ahmed, and R. N. Cooney Interleukin-1 inhibits the induction of insulin-like growth factor-I by growth hormone in CWSV-1 hepatocytes Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G227 - G239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fruchtman, J. G. Simmons, C. Z. Michaylira, M. E. Miller, C. J. Greenhalgh, D. M. Ney, and P. K. Lund Suppressor of cytokine signaling-2 modulates the fibrogenic actions of GH and IGF-I in intestinal mesenchymal cells Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G342 - G350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Held, W. Cosme-Blanco, L. M. Difedele, E. L. Bonkowski, R. K. Menon, and L. A. Denson Alterations in growth hormone receptor abundance regulate growth hormone signaling in murine obstructive cholestasis Am J Physiol Gastrointest Liver Physiol, May 1, 2005; 288(5): G986 - G993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Dunn, M. Bjornholm, S. H. Bates, Z. Chen, M. Seifert, and M. G. Myers Jr. Feedback Inhibition of Leptin Receptor/Jak2 Signaling via Tyr1138 of the Leptin Receptor and Suppressor of Cytokine Signaling 3 Mol. Endocrinol., April 1, 2005; 19(4): 925 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Rowland, A. M. Lichanska, L. M. Kerr, M. White, E. M. d'Aniello, S. L. Maher, R. Brown, R. D. Teasdale, P. G. Noakes, and M. J. Waters In Vivo Analysis of Growth Hormone Receptor Signaling Domains and Their Associated Transcripts Mol. Cell. Biol., January 1, 2005; 25(1): 66 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kotokorpi, C. Gardmo, C. S. Nystrom, and A. Mode Activation of the Glucocorticoid Receptor or Liver X Receptors Interferes with Growth Hormone-Induced akr1b7 Gene Expression in Rat Hepatocytes Endocrinology, December 1, 2004; 145(12): 5704 - 5713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Brelje, L. E. Stout, N. V. Bhagroo, and R. L. Sorenson Distinctive Roles for Prolactin and Growth Hormone in the Activation of Signal Transducer and Activator of Transcription 5 in Pancreatic Islets of Langerhans Endocrinology, September 1, 2004; 145(9): 4162 - 4175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, L. M. Gronning, P. O. Anderson, S. Li, K. Edvardsen, J. Johnston, D. Kioussis, P. R. Shepherd, and P. Wang Insulin Induces SOCS-6 Expression and Its Binding to the p85 Monomer of Phosphoinositide 3-Kinase, Resulting in Improvement in Glucose Metabolism J. Biol. Chem., August 13, 2004; 279(33): 34107 - 34114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Miquet, A. I. Sotelo, A. Bartke, and D. Turyn Suppression of Growth Hormone (GH) Janus Tyrosine Kinase 2/Signal Transducer and Activator of Transcription 5 Signaling Pathway in Transgenic Mice Overexpressing Bovine GH Endocrinology, June 1, 2004; 145(6): 2824 - 2832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Goldshmit, C. E. Walters, H. J. Scott, C. J. Greenhalgh, and A. M. Turnley SOCS2 Induces Neurite Outgrowth by Regulation of Epidermal Growth Factor Receptor Activation J. Biol. Chem., April 16, 2004; 279(16): 16349 - 16355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yoshimura, H. M. M. Ohishi, D. Aki, and T. Hanada Regulation of TLR signaling and inflammation by SOCS family proteins J. Leukoc. Biol., March 1, 2004; 75(3): 422 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Zoubiane, A. Valentijn, E. T. Lowe, N. Akhtar, S. Bagley, A. P. Gilmore, and C. H. Streuli A role for the cytoskeleton in prolactin-dependent mammary epithelial cell differentiation J. Cell Sci., January 15, 2004; 117(2): 271 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Benekli, M. R. Baer, H. Baumann, and M. Wetzler Signal transducer and activator of transcription proteins in leukemias Blood, April 15, 2003; 101(8): 2940 - 2954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Senn, P. J. Klover, I. A. Nowak, T. A. Zimmers, L. G. Koniaris, R. W. Furlanetto, and R. A. Mooney Suppressor of Cytokine Signaling-3 (SOCS-3), a Potential Mediator of Interleukin-6-dependent Insulin Resistance in Hepatocytes J. Biol. Chem., April 11, 2003; 278(16): 13740 - 13746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Denson, M. A. Held, R. K. Menon, S. J. Frank, A. F. Parlow, and D. L. Arnold Interleukin-6 inhibits hepatic growth hormone signaling via upregulation of Cis and Socs-3 Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G646 - G654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Du, G. P. Frick, L.-R. Tai, A. Yoshimura, and H. M. Goodman Interaction of the Growth Hormone Receptor with Cytokine-Induced Src Homology Domain 2 Protein in Rat Adipocytes Endocrinology, March 1, 2003; 144(3): 868 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Leung, N. Doyle, M. Ballesteros, K. Sjogren, C. K. W. Watts, T. H. Low, G. M. Leong, R. J. M. Ross, and K. K. Y. Ho Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2 PNAS, February 4, 2003; 100(3): 1016 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Giordanetto and R. T. Kroemer A three-dimensional model of Suppressor Of Cytokine Signalling 1 (SOCS-1) Protein Eng. Des. Sel., February 1, 2003; 16(2): 115 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Liu, L. Robillard, B. Banihashemi, and P. R. Albert Growth Hormone-induced Diacylglycerol and Ceramide Formation via Galpha i3 and Gbeta gamma in GH4 Pituitary Cells. POTENTIATION BY DOPAMINE-D2 RECEPTOR ACTIVATION J. Biol. Chem., December 6, 2002; 277(50): 48427 - 48433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Greenhalgh, D. Metcalf, A. L. Thaus, J. E. Corbin, R. Uren, P. O. Morgan, L. J. Fabri, J.-G. Zhang, H. M. Martin, T. A. Willson, et al. Biological Evidence That SOCS-2 Can Act Either as an Enhancer or Suppressor of Growth Hormone Signaling J. Biol. Chem., October 18, 2002; 277(43): 40181 - 40184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-E. Kong, S. M. Firth, R. C. Baxter, and P. J. D. Delhanty Regulation of the acid-labile subunit in sustained endotoxemia Am J Physiol Endocrinol Metab, October 1, 2002; 283(4): E692 - E701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Morales, M. H. Faulds, U. J. Lindgren, and L.-A. Haldosen 1alpha ,25-Dihydroxyvitamin D3 Inhibits GH-induced Expression of SOCS-3 and CIS and Prolongs Growth Hormone Signaling via the Janus Kinase (JAK2)/Signal Transducers and Activators of Transcription (STAT5) System in Osteoblast-like Cells J. Biol. Chem., September 13, 2002; 277(38): 34879 - 34884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. E. Timsit and D. S. Riddick Stimulation of Hepatic Signal Transducer and Activator of Transcription 5b by GH Is Not Altered by 3-Methylcholanthrene Endocrinology, September 1, 2002; 143(9): 3284 - 3294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Ronn, J. A. Hansen, K. Lindberg, A. E. Karlsen, and N. Billestrup The Effect of Suppressor of Cytokine Signaling 3 on GH Signaling in {beta}-Cells Mol. Endocrinol., September 1, 2002; 16(9): 2124 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ji, S. J. Frank, and J. L. Messina Growth Hormone-induced Differential Desensitization of STAT5, ERK, and Akt Phosphorylation J. Biol. Chem., August 9, 2002; 277(32): 28384 - 28393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Krebs, R. T. Uren, D. Metcalf, S. Rakar, J.-G. Zhang, R. Starr, D. P. De Souza, K. Hanzinikolas, J. Eyles, L. M. Connolly, et al. SOCS-6 Binds to Insulin Receptor Substrate 4, and Mice Lacking the SOCS-6 Gene Exhibit Mild Growth Retardation Mol. Cell. Biol., July 1, 2002; 22(13): 4567 - 4578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tonko-Geymayer, O. Goupille, M. Tonko, C. Soratroi, A. Yoshimura, C. Streuli, A. Ziemiecki, R. Kofler, and W. Doppler Regulation and Function of the Cytokine-Inducible SH-2 Domain Proteins, CIS and SOCS3, in Mammary Epithelial Cells Mol. Endocrinol., July 1, 2002; 16(7): 1680 - 1695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Greenhalgh, P. Bertolino, S. L. Asa, D. Metcalf, J. E. Corbin, T. E. Adams, H. W. Davey, N. A. Nicola, D. J. Hilton, and W. S. Alexander Growth Enhancement in Suppressor of Cytokine Signaling 2 (SOCS-2)-Deficient Mice Is Dependent on Signal Transducer and Activator of Transcription 5b (STAT5b) Mol. Endocrinol., June 1, 2002; 16(6): 1394 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ungureanu, P. Saharinen, I. Junttila, D. J. Hilton, and O. Silvennoinen Regulation of Jak2 through the Ubiquitin-Proteasome Pathway Involves Phosphorylation of Jak2 on Y1007 and Interaction with SOCS-1 Mol. Cell. Biol., May 15, 2002; 22(10): 3316 - 3326. [Abstract] [Full Text] [PDF]
|
|
