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Cellular and Molecular Life Sciences

, Volume 71, Issue 17, pp 3297–3310 | Cite as

SOCS proteins in regulation of receptor tyrosine kinase signaling

  • Julhash U. Kazi
  • Nuzhat N. Kabir
  • Amilcar Flores-Morales
  • Lars Rönnstrand
Review

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.

Keywords

SOCS1 SOCS2 SOCS3 SOCS6 FLT3 KIT INSR IGF1R CSF1R PDGFR 

Notes

Acknowledgments

This research was funded by the Swedish Cancer Society (LR), the Swedish Childhood Cancer Foundation (LR), the Swedish Research Council (LR), ALF governmental clinical grant (LR), Stiftelsen Olle Engkvist Byggmästare (JUK), the Royal Physiographic Society in Lund (JUK), Ollie och Elof Ericssons Stiftelse (JUK) and The Lars Hierta Memorial Foundation (JUK).

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

18_2014_1619_MOESM1_ESM.pdf (678 kb)
Supplementary material 1 (PDF 678 kb)

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Julhash U. Kazi
    • 1
    • 2
    • 3
  • Nuzhat N. Kabir
    • 3
  • Amilcar Flores-Morales
    • 4
  • Lars Rönnstrand
    • 1
    • 2
  1. 1.Division of Translational Cancer ResearchLund UniversityLundSweden
  2. 2.Lund Stem Cell CenterLund UniversityLundSweden
  3. 3.Laboratory of Computational BiochemistryKN Biomedical Research InstituteBarisalBangladesh
  4. 4.Novo Nordisk Foundation Center for Protein Research, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark

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