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Tyrosine kinase report

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Tyrosine kinase report

  1. 1. TYROSINE KINASE by: Mary Jean D. Somcio
  2. 2. INTRODUCTION• Protein kinases are a group of enzymes that possess a catalytic subunit that transfers the gamma (terminal) phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function.
  3. 3. HOW SIGNAL IS PASS INSIDE THE CELLL?• Signal Transduction - a basic process involving the conversion of a signal from outside the cell to a functional change within the cell
  4. 4. SIGNAL MOLECULES & RECEPTORS • 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.
  5. 5. CATEGORIES OF PROTEIN KINASES Classified into three different categories: 1. Kinases that specifically phosphorylate tyrosine residues 2. Kinases that phosphorylate serine and threonine residues, and 3. Kinases with activity toward all three residues.
  6. 6. SIGNALING THROUGH ENZYME-LINKED CELL-SURFACE RECEPTORSSix classes:1. Receptor tyrosine kinases2. Tyrosine kinase-associated receptors3. Receptor like tyrosine phosphatases4. Receptor serine/threonine kinases5. Receptor guanylyl cyclases6. Histidine-kinase-associated receptors
  7. 7. WHAT IS A TYROSINE KINASE? A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein.
  8. 8. FAMILIESApproximately 2000 kinases are known.Among them 90 are tyrosine kinasesThe tyrosine kinases are divided into twomain families: – the trans membrane receptor- linked kinases – those that are cytoplasmic proteins
  9. 9. TYPES OF TYROSINE KINASESTyrosine kinases can be furthersubdivided into:1. Receptor tyrosine kinases eg: EGFR, PDGFR, FGFR2. Non-receptor tyrosine kinases eg: SRC, ABL, FAK and Janus kinase
  10. 10. RECEPTOR58 receptor tyrosine kinases (RTKs) are known, grouped into 20 subfamilies.These are involved in: growth Differentiation Metabolism Adhesion Motility death
  11. 11. CYTOPLASMIC/NON-RECEPTOR  32 cytoplasmic protein tyrosine kinases are also known as PTKs.  First non-receptor tyrosine kinase identified was the v-src oncogenic protein
  12. 12. RECEPTOR TYROSINE KINASE RTK is like a communication device, since these membrane proteins transmit signals from the cell’s environment into the cell.Tyrosine-kinase receptor is effective when the cell needs to regulate and coordinate a variety of activities and trigger several signal pathways at once.
  13. 13. TYROSINE KINASE STRUCTURE Extracellular Domain Transmembrane Domain TK Intracellular Domain
  14. 14. MECHANISM OF TYROSINE KINASEProtein/hormone binding with extracellular domain
  15. 15. MECHANISM OF TYROSINE KINASE
  16. 16. MECHANISM OF TYROSINE KINASE
  17. 17. MECHANISM OF TYROSINE KINASE
  18. 18. MECHANISM OF TYROSINE KINASE
  19. 19. MECHANISM OF TYROSINE KINASE
  20. 20. MECHANISM OF TYROSINE KINASE
  21. 21. MECHANISM OF TYROSINE KINASE
  22. 22. CLASSIFICATION OF RTKsThere are almost 20 classes of RTKs. - EGF receptor - Insuline receptor - FGF receptors - PDGF - VEGF receptor - NGF - ephrins (Eph)
  23. 23. EPIDERMAL GROWTH FACTORA growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR.Human EGF is a 6045-Da protein with 53 amino acid residues and three intramolecular disulfide bonds.
  24. 24. INSULINE RECEPTOR (IR)A transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of tyrosine kinase receptors.
  25. 25. INSULINE RECEPTOR (IR)EFFECT OF INSULIN ON GLUCOSE UPTAKE AND METABOLISM Insulin binds to its receptor (1), which, in turn, starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5), and fatty acid synthesis (6)
  26. 26. FIBROBLAST GROWTH FACTORFamily of growth factors involved in angiogenesis, wound healing, and embryonic development.The FGFs are heparin-binding proteins and interactions with cell- surface-associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction.
  27. 27. PLATELET-DERIVED GROWTH FACTORPotent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells.In chemical terms, platelet-derived growth factor is dimeric glycoprotein composed of two A (- AA) or two B (-BB) chains or a combination of the two (-AB).
  28. 28. NERVE GROWTH FACTOR A member of a family of small secreted proteins known as neurotropins that function as signaling molecules.
  29. 29. EPHRINS (Eph)The Eph family of receptors is the largest known subfamily of receptor tyrosine kinases.The ligands are called ephrins.
  30. 30. VASCULAR ENDOTHELIAL FACTORA signal protein produced by cells that stimulates vasculogenesis and angiogenesis.It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.

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