Saturday, October 17, 2009

receptor based tyrosinekinases-cellsignalling-7th chapter-cellbiology-btechbiotechnology-2-1-jntu syllabus

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. Tyrosine kinases are a subgroup of the larger class of protein kinases. Phosphorylation of proteins by kinases is an important mechanism in signal transduction for regulation of enzyme activity.
There are over 100 3D structures of tyrosine kinases available at the Protein Data Bank. An example is PDB 1IRK, the crystal structure of the tyrosine kinase domain of the human insulin receptor.
Most tyrosine kinases have an associated protein tyrosine phosphatase.
The tyrosine kinases are divided into two groups:

* those that are cytoplasmic proteins.
* the transmembrane receptor-linked kinases.

receptor based tyrosine kinases:
Receptor tyrosine kinases (RTK)s are the high affinity cell surface receptors for many polypeptide growth factors, cytokines and hormones. Of the ninety unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins.[1] Receptor tyrosine kinases have been shown to be not only key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer.
types of receptor tyrosine kinases:
1. RTK class I (EGF receptor family)
2. RTK class II (Insulin receptor family)
3. RTK class III (PDGF receptor family)
4. RTK class IV (FGF receptor family)
5. RTK class V (VEGF receptors family)
6. RTK class VI (HGF receptor family)
7. RTK class VII (Trk receptor family)
8. RTK class IX (AXL receptor family)
9. RTK class X (LTK receptor family)
10. RTK class XI (TIE receptor family)
11. RTK class XII (ROR receptor family)
12. RTK class XIII (DDR receptor family)
13. RTK class XV (KLG receptor family)
14. RTK class XVI (RYK receptor family)
15. RTK class XVII (MuSK receptor family)

structure of receptor tyrosine kinase:
The extracellular N-terminal region exhibits a variety of conserved elements including immunoglobulin (Ig)-like or epidermal growth factor (EGF)-like domains, fibronectin type III repeats or cysteine-rich regions that are characteristic for each subfamily of RTKs; these domains contain primarily a ligand-binding site, which binds extracellular ligands e.g. a particular growth factor or hormone.[5] The intracellular C-terminal region displays the highest level of conservation and comprises catalytic domains responsible for the kinase activity of these receptors, which catalyses receptor autophosphorylation and tyrosine phosphorylation of RTK substrates

Kinase activity
When a growth factor binds to the extracellular domain of an RTK, its dimerization is triggered with other adjacent RTKs. Dimerization leads to a rapid activation of the protein's cytoplasmic kinase domains, the first substrate for these domains being the receptor itself. The activated receptor as a result then becomes autophosphorylated on multiple specific intracellular tyrosine residues.thus leads to signal transduction process and finally experession of thatr particular gene.

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