Advanced

SOCS proteins in regulation of receptor tyrosine kinase signaling.

Kazi, Julhash U. LU ; Kabir, Nuzhat N; Flores-Morales, Amilcar and Rönnstrand, Lars LU (2014) In Cellular and Molecular Life Sciences 71(17). p.3297-3310
Abstract
Receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many in this family of kinases are overexpressed or mutated in human malignancies and thus became an attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressors of cytokine signaling (SOCS) family proteins are well-known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7, and cytokine-inducible SH2-containing protein (CIS). A key feature of this family of proteins is the presence of an SH2... (More)
Receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many in this family of kinases are overexpressed or mutated in human malignancies and thus became an attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressors of cytokine signaling (SOCS) family proteins are well-known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7, and cytokine-inducible SH2-containing protein (CIS). A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS-encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion, SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs can sometimes bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus, apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cellular and Molecular Life Sciences
volume
71
issue
17
pages
3297 - 3310
publisher
Birkhaüser
external identifiers
  • pmid:24705897
  • wos:000340554300008
  • scopus:84906216359
ISSN
1420-9071
DOI
10.1007/s00018-014-1619-y
language
English
LU publication?
yes
id
7e171c74-0484-4e47-9c63-3a3477e60342 (old id 4430756)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24705897?dopt=Abstract
date added to LUP
2014-05-06 19:45:07
date last changed
2017-11-05 03:02:03
@article{7e171c74-0484-4e47-9c63-3a3477e60342,
  abstract     = {Receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many in this family of kinases are overexpressed or mutated in human malignancies and thus became an attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressors of cytokine signaling (SOCS) family proteins are well-known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7, and cytokine-inducible SH2-containing protein (CIS). A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS-encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion, SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs can sometimes bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus, apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways.},
  author       = {Kazi, Julhash U. and Kabir, Nuzhat N and Flores-Morales, Amilcar and Rönnstrand, Lars},
  issn         = {1420-9071},
  language     = {eng},
  number       = {17},
  pages        = {3297--3310},
  publisher    = {Birkhaüser},
  series       = {Cellular and Molecular Life Sciences},
  title        = {SOCS proteins in regulation of receptor tyrosine kinase signaling.},
  url          = {http://dx.doi.org/10.1007/s00018-014-1619-y},
  volume       = {71},
  year         = {2014},
}