Biosignaling and the KEGG Database

Exercise Goals

• Learn how to use the KEGG database.
• Describe the relationships between receptors, kinases, and cellular functions in biosignaling.

Resources & Websites

• Kyoto Encyclopedia of Genes and Genomes (KEGG):

http://www.kegg.jp

• Description of the KEGG database:

http://www.kegg.jp/kegg/kegg1.html

Exercise

As inferred from Chapter 10, the many processes of biosignaling represent a complex fabric of interconnected pathways that regulate cellular function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) provides a means to visualize these pathways and to obtain information about the associated proteins and genes. In this exercise, information from the KEGG databases will be analyzed to explore the insulin and MAPK signaling pathways.

Instructions

1. Go to http://www.kegg.jp.
2. For Questions 1-8 from the assessment section, use Steps 3-11.
3. Search for "Insulin."
4. Under the "KEGG PATHWAY" heading, click on the "Insulin Signaling Pathway" link, which is entitled "map04910."
5. This action will load the KEGG page "map04910," which provides a description of the insulin signaling pathway, a map of the connecting pathways, and several associated references.
6. Read the description of the pathway.
7. Click on the image of the map in the "Pathway map" section of the page.
8. This action loads a map of the known pathways that relate to insulin biosignaling, where each box represents an enzyme or protein (and related gene) that is involved in the holistic biosignaling pathway.
9. In the KEGG pathway map:
10. Each hyperlinked box leads to the specific KEGG page for that protein, which includes gene information, related pathways, sequence data, structure images, references, and more.
11. Each hyperlinked oval leads to the specific KEGG page for that pathway.
12. Using the drop down menu on the top left of the page, choose "Homo sapiens (humans)" and click on "Go."
13. Take note of the boxes on the map that change to a green color, which indicates that this protein/gene is found in the chosen organism.
14. For Questions 9-13 from the assessment section, use Steps 13-15.
15. Go back to the KEGG home page and search for "MAPK."
16. Under the KEGG PATHWAY heading, click on the link for the MAPK signaling pathway from yeast ("map04011").
17. Repeat Steps 6 and 7.
18. Use this information to answer the assessment questions.

Assessment Questions

1.What does the box labeled "INSR" refer to, and how many amino acids are found in this protein?

1. Insulin; 1382
2. Insulin receptor; 1382
3. Insulin; 4149
4. Insulin receptor; 4149

2.For INSR, the membrane-bound location of this protein is __________________, while the dephosphorylated form of this protein, the active (or sensitized) state, is indicated by the ____ symbol.

1. indicated by the 2 thick parallel gray lines on the map; +p
2. indicated by the 2 thick parallel gray lines on the map; -p
3. directly stated in the KEGG page for INSR; +p
4. directly stated in the KEGG page for INSR; -p

3.Which protein serves as a branching point for the activation of glycolysis, antilipolysis (or inhibition of fatty acid release from the adipose tissue), antiapoptosis, and glycogenesis?

1. RAC serine/threonine-protein kinase
2. 3-phosphoinositide dependent protein kinase-1
3. insulin receptor substrate 1
4. phosphatidylinositol-3,4,5-trisphosphate

4.The insulin-dependent activation of protein synthesis requires activation of mTOR by _____, which proceeds forward by _____________ of p70 ribosomal S6 kinase.

1. phosphatidylinositol-3,4,5-trisphosphate; phosphorylation
2. phosphatidylinositol-3,4,5-trisphosphate; dephosphorylation
3. phosphoinositide-3-kinase; phosphorylation
4. phosphoinositide-3-kinase; dephosphorylation