Suppressors Of Cytokine Signalling

  • INTREGATIVE PROJECT

    By Hannah Njoroge,kim peyton and Joseph Jean

    BIOINFORMATIC PROGRAM WWW.SUGARLAND.UH.EDU

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    Cytokines

    "Cytokine" is a word that comes from cyto- a combining form meaning "cell" - and -kinin - a combining form used in naming hormones, especially peptide hormones (e.g., bradykinin). Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced de novo in response to an immune stimulus.

    A. Role and function

  • Orthologs are small proteins part of an extracellular signaling network Bind to cell receptors Initiate intracellular cascade (i.e. kinase)Results in production of transcription factors

  • PROPERTIES OF CYTOKINES

  • Primary Structure
  • Access NCBI or PubMed WWW.NCBI.NIM.GOV In the query box type: suppressors of cytokine signaling SOCS proteins This brings up a screen with several articles. Page down to the article by Alexander WS, Hilton DJ. Select "Related Articles" on the right side of the screen. Select the article by Hanada, Kinjyo, et.al titled " Negative regulation of cytokine signaling by CIS/SOCS family proteins and their roles in inflammatory diseases". The abstract is a good review. Open the full article available at Springer Link. On the Springer Link page, open by selecting the "Local HTML (non-pagenated) tab. This brings up the full article. It is very good. By scrolling down, graphics showing the CIS/SOCS family are displayed. Further down is a mechanism describing the negative feedback regulation of the SOCS gene by cytokine signaling.

  • Secondary Structure and tertiary structure.
  • Go back to NCBI, and select Map Viewer. On Map Viewer, we can then type in any of the SOCS proteins such as SOCS1, SOCS2, SOCS4, etc. This brings up the chromosomes containing the genes/ By selecting the gene, the SOCS proteins appear. From this, we can then scroll to the amino acid sequence, copy, and paste into BLAST. In BLAST there are several points to discuss such as the CDD, SOCS Box, and others.
  • A HREF= "www.expasy.org" WWW.EXPASY.ORG This site is one of the world's first protein databases created and contains much useful information. The panel on the right side of the page has a box containing many selections. Choose "Primary Structure" Select the first listing, and paste the same amino acid sequence used in the BLAST search. Useful information about the molecular weight, percentage of each amino acid in the SOCS protein, and other facts are given. Go back and then select "Secondary Structure". Paste the amino acid sequence. A secondary structure description in provided listing helix regions and other known regions.
  • Seven different SOCS proteins

  • SOCS 1 inhibition.
      1. a & g interferon suppression leads to KO Mice die with 3-weeks of birth 2. Methylated in promoter region in T-cell leukemia leads to
        Multiple myeloma >Colorectal cancer Pancreatic cancer
      3. Over expression inhibits some cervical cancers

    OTHER SOCS PROTEINS

  • SOCS 2 Inhibited in gigantism
  • SOCS 3 Inhibited in lung cancer
  • SOCS 4 No known disease
  • SOCS 5 No known disease
  • SOCS 6 High levels in chronic myelogenous leukemia
  • SOCS 7 KO mice fatal hydrocephalus
  • Phylogenic tree

    The SOCS (Suppressors Of Cytokine Signalling) proteins are more narrrow in scope than prions and mitogens and may allow us to prepare a more focused Bioinformatics Application Project. After looking through the NCBI site, home page? there is information on SOCS- related dieseses, information on conserved SOCS domains and amino acid sequences. There are seven or eight SOCS proteins, and each one seems to have a different target. If you type in "SOCS Protein" in the www.ncbi.nlm.nih.govWWW.NCBI.ORG there is quite a variety of information topics available. I completed a BLAST serach for one of the SOCS proteins and found the SOCS gene to be located on more than one chromosome. Also, there is some infomation in our text on p. 586 about SOCS proteins and their function.


  • CONLUSION
  • By functioning in feedback inhibition, suppressors of cytokine signaling (SOCS) proteins regulate cytokine activity. The seven known SOCS proteins play an essential role in maintaining homeostasis. Methylation of SOCS genes is evident in a wide range of pathogenic conditions such as pancreatic cancer, colorectal cancer, and multiple myeloma. Treatment with SOCS proteins may play a theraputic role in cancer control. However, more research is needed to better understand the role of SOCS proteins in health and disease.

  • REFERENCES:

    1. TEXTBOOK: Molecular Cell Biology (Fifth Edition), Lodish, Berk, Zipursky, Matsudaira, Baltimore, and Darnell href="mailto:paul@mcfedries.com">WWW.UHV.EDU.