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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2. A basic process involving the
conversion of a signal from outside
the cell to a functional change within
the cell
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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.
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4. Six classes:
1. Receptor tyrosine kinases
2. Tyrosine kinase-associated receptors
3. Receptor like tyrosine phosphatases
4. Receptor serine/threonine kinases
5. Receptor guanylyl cyclases
6. Histidine-kinase-associated receptors
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6. 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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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
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8.  58 receptor tyrosine kinases (RTKs) are
known, grouped into 20 subfamilies.
 These are involved in:
 growth
 Differentiation
 Metabolism
 Adhesion
 Motility
 death
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9.  32 cytoplasmic protein tyrosine kinases are
known also known as PTKs.
 first non-receptor tyrosine kinase identified
was the v-src oncogenic protein.
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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?
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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.
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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.
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13. Phsphorylated Tyrosine Serve as docking sites for protein with SH2 domains
(Src homology region). 13

14. 1. Protein/hormone binding with extracellular
domain
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15. 2. The tyrosine kinase domains phosphorylate the C terminal
tyrosine residues
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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.
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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..
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18. 5. Activated ras then causes the activation of a cellular kinase
called raf-1.
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19. 6. Raf-1 kinase then phosphorylates another cellular kinase
called MEK. This cause the activation of MEK.
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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.
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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.
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22. There are almost 20 classes of RTKs.
EGFreceptor
Insuline receptor
FGF receptors
PDGF
VEGF receptor
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