Suppressors of cytokine signaling (SOCS)

Negative regulators of signal transduction

Warren S. Alexander, Robyn Starr, Donald Metcalf, Sandra E. Nicholson, Alison Farley, Andrew G. Elefanty, Marta Brysha, Benjamin T. Kile, Rachel Richardson, Manuel Baca, Jian Guo Zhang, Tracy A. Willson, Elizabeth M. Viney, Naomi S. Sprigg, Steven Rakar, Jason Corbin, Sandra Mifsud, Ladina Dirago, Dale Cary, Nicos A. Nicola & 1 others Douglas J. Hilton

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS- 1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but faded to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.

Original languageEnglish
Pages (from-to)588-592
Number of pages5
JournalJournal of leukocyte biology
Volume66
Issue number4
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • JAK
  • STAT

Cite this

Alexander, W. S., Starr, R., Metcalf, D., Nicholson, S. E., Farley, A., Elefanty, A. G., ... Hilton, D. J. (1999). Suppressors of cytokine signaling (SOCS): Negative regulators of signal transduction. Journal of leukocyte biology, 66(4), 588-592.
Alexander, Warren S. ; Starr, Robyn ; Metcalf, Donald ; Nicholson, Sandra E. ; Farley, Alison ; Elefanty, Andrew G. ; Brysha, Marta ; Kile, Benjamin T. ; Richardson, Rachel ; Baca, Manuel ; Zhang, Jian Guo ; Willson, Tracy A. ; Viney, Elizabeth M. ; Sprigg, Naomi S. ; Rakar, Steven ; Corbin, Jason ; Mifsud, Sandra ; Dirago, Ladina ; Cary, Dale ; Nicola, Nicos A. ; Hilton, Douglas J. / Suppressors of cytokine signaling (SOCS) : Negative regulators of signal transduction. In: Journal of leukocyte biology. 1999 ; Vol. 66, No. 4. pp. 588-592.
@article{15b646b312af413b9868030344fcd5c3,
title = "Suppressors of cytokine signaling (SOCS): Negative regulators of signal transduction",
abstract = "SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS- 1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but faded to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.",
keywords = "JAK, STAT",
author = "Alexander, {Warren S.} and Robyn Starr and Donald Metcalf and Nicholson, {Sandra E.} and Alison Farley and Elefanty, {Andrew G.} and Marta Brysha and Kile, {Benjamin T.} and Rachel Richardson and Manuel Baca and Zhang, {Jian Guo} and Willson, {Tracy A.} and Viney, {Elizabeth M.} and Sprigg, {Naomi S.} and Steven Rakar and Jason Corbin and Sandra Mifsud and Ladina Dirago and Dale Cary and Nicola, {Nicos A.} and Hilton, {Douglas J.}",
year = "1999",
language = "English",
volume = "66",
pages = "588--592",
journal = "Journal of leukocyte biology",
issn = "0741-5400",
publisher = "Society for Leukocyte Biology",
number = "4",

}

Alexander, WS, Starr, R, Metcalf, D, Nicholson, SE, Farley, A, Elefanty, AG, Brysha, M, Kile, BT, Richardson, R, Baca, M, Zhang, JG, Willson, TA, Viney, EM, Sprigg, NS, Rakar, S, Corbin, J, Mifsud, S, Dirago, L, Cary, D, Nicola, NA & Hilton, DJ 1999, 'Suppressors of cytokine signaling (SOCS): Negative regulators of signal transduction', Journal of leukocyte biology, vol. 66, no. 4, pp. 588-592.

Suppressors of cytokine signaling (SOCS) : Negative regulators of signal transduction. / Alexander, Warren S.; Starr, Robyn; Metcalf, Donald; Nicholson, Sandra E.; Farley, Alison; Elefanty, Andrew G.; Brysha, Marta; Kile, Benjamin T.; Richardson, Rachel; Baca, Manuel; Zhang, Jian Guo; Willson, Tracy A.; Viney, Elizabeth M.; Sprigg, Naomi S.; Rakar, Steven; Corbin, Jason; Mifsud, Sandra; Dirago, Ladina; Cary, Dale; Nicola, Nicos A.; Hilton, Douglas J.

In: Journal of leukocyte biology, Vol. 66, No. 4, 1999, p. 588-592.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - Suppressors of cytokine signaling (SOCS)

T2 - Negative regulators of signal transduction

AU - Alexander, Warren S.

AU - Starr, Robyn

AU - Metcalf, Donald

AU - Nicholson, Sandra E.

AU - Farley, Alison

AU - Elefanty, Andrew G.

AU - Brysha, Marta

AU - Kile, Benjamin T.

AU - Richardson, Rachel

AU - Baca, Manuel

AU - Zhang, Jian Guo

AU - Willson, Tracy A.

AU - Viney, Elizabeth M.

AU - Sprigg, Naomi S.

AU - Rakar, Steven

AU - Corbin, Jason

AU - Mifsud, Sandra

AU - Dirago, Ladina

AU - Cary, Dale

AU - Nicola, Nicos A.

AU - Hilton, Douglas J.

PY - 1999

Y1 - 1999

N2 - SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS- 1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but faded to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.

AB - SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS- 1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but faded to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.

KW - JAK

KW - STAT

UR - http://www.scopus.com/inward/record.url?scp=0032836015&partnerID=8YFLogxK

M3 - Review Article

VL - 66

SP - 588

EP - 592

JO - Journal of leukocyte biology

JF - Journal of leukocyte biology

SN - 0741-5400

IS - 4

ER -

Alexander WS, Starr R, Metcalf D, Nicholson SE, Farley A, Elefanty AG et al. Suppressors of cytokine signaling (SOCS): Negative regulators of signal transduction. Journal of leukocyte biology. 1999;66(4):588-592.