Receptor tyrosine kinase

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A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein.

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Receptor tyrosine kinase

  1. 1. 1
  2. 2. A basic process involving the conversion of a signal from outsidethe cell to a functional change within the cell 2
  3. 3. • A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule.• When ligands (small molecules that bind specifically to a larger molecule) attach to the receptor protein, the receptor typically undergoes a change in shape. 3
  4. 4. Six classes:1. Receptor tyrosine kinases2. Tyrosine kinase-associated receptors3. Receptor like tyrosine phosphatases4. Receptor serine/threonine kinases5. Receptor guanylyl cyclases6. Histidine-kinase-associated receptors 4
  5. 5. 5
  6. 6. A tyrosine kinase is an enzyme that cantransfer a phosphate group from ATP to atyrosine residue in a protein. 6
  7. 7. • Approximately 2000 kinases are known.among them 90 are tyrosine kinases• The tyrosine kinases are divided into two main families: – the transmembrane receptor-linked kinases – those that are cytoplasmic proteins 7
  8. 8.  58 receptor tyrosine kinases (RTKs) are known, grouped into 20 subfamilies. These are involved in:  growth  Differentiation  Metabolism  Adhesion  Motility  death 8
  9. 9.  32 cytoplasmic protein tyrosine kinases are known also known as PTKs. first non-receptor tyrosine kinase identified was the v-src oncogenic protein. 9
  10. 10.  RTK as like a communication device, since these membrane proteins transmit signals from the cell’s environment into the cell. Event X outside the cell is translated into Event Y inside the cell. Specifically, the signaling molecules (such as hormones) bind the extracellular portion of the receptor protein. This binding event is then somehow communicated to the contents inside the cell. But how? 10
  11. 11. Tyrosine-kinase receptor is effective when the cell needs to regulate and coordinate a variety of activities and trigger several signal pathways at once. 11
  12. 12. • Extracellular ligand binding domain.• Intracellular tyrosine kinase domain, with amino acid sequences in ATP binding and substrate binding regions• Intracellular regulatory domain.• Transmembrane domain. 12
  13. 13. Phsphorylated Tyrosine Serve as docking sites for protein with SH2 domains(Src homology region). 13
  14. 14. 1. Protein/hormone binding with extracellular domain 14
  15. 15. 2. The tyrosine kinase domains phosphorylate the C terminal tyrosine residues 15
  16. 16. 3. This phosphorylation produces binding sites for proteins with SH2 domains. GRB2 is one of these proteins. GRB2, with SOS bound to it, then binds to the receptor complex. This causes the activation of SOS. 16
  17. 17. 4. SOS is a guanyl nucleotide-release protein (GNRP). When this is activated, it causes certain G proteins to release GDP and exchange it for GTP. Ras is one of these proteins. When ras has GTP bound to it, it becomes active.. 17
  18. 18. 5. Activated ras then causes the activation of a cellular kinase called raf-1. 18
  19. 19. 6. Raf-1 kinase then phosphorylates another cellular kinase called MEK. This cause the activation of MEK. 19
  20. 20. 7. Activated MEK then phosphorylates another protein kinase called MAPK causing its activation. This series of phosphylating activations is called a kinase cascade. It results in amplification of the signal. 20
  21. 21. 8. Among the final targets of the kinase cascade are transcriptions factors (fos and jun showed here). Phosphorylation of these proteins causes them to become active and bind to the DNA, causing changes in gene transcription. 21
  22. 22. There are almost 20 classes of RTKs.EGFreceptorInsuline receptorFGF receptorsPDGFVEGF receptor 22
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