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๐Ÿ“š > Physiology > General Physiology > Signal Transduction_>

Receptor Tyrosine Kinase and MAPK Pathway



Receptor Tyrosine Kinase (RTK)

  • Types of catalytic receptors. i.e. receptor molecule also has catalytic activity.

  • Most RTKs are single-pass transmembrane proteins.

  • Have ligand-binding domain on the extracellular side.

  • Have tyrosine kinase domain on the intracellular side.

  • Example:

  • Receptors for insulin.

  • Receptors for growth factors e.g. EGF, PDGF.


Resting-State

  • Receptor molecules exist in monomeric form.


Activation and Signaling

Binding of the ligand

โ†“

Two receptor molecules come together and form a dimer

โ†“

Kinase domain of one receptor molecule phosphorylates tyrosine residues on the other receptor molecule

โ†“

Formation of phosphotyrosine (pY) motifs

โ†“

Binding of SH2 domain-containing protein. E.g:

โ€ข GRB2 โŸถ Leads to MAPK pathway

โ€ข PI3K โŸถ Leads to PI3K pathway


MAPK Pathway

Process from activation of receptor to the recruitment of GRB2 as explained above

โ†“

GRB2 attracts SOS (Son of Sevenless)

โ†“

SOS activates Ras

โ†“

Ras activates Raf-1 (MAP kinase kinase kinase)

โ†“

Raf-1 activates MEK (MAP kinase kinase)

โ†“

MEK activates MAPK (MAP kinase)

  • MAPK phosphorylates:

  • Proteins involved in cytoskeletal assembly and cell-matrix interaction โŸถ change in cell morphology and cell migration.

  • Transcription factors โŸถ Increase or decrease in transcription of genes involved in cell survival and proliferation.


PI3K Pathway

Process from activation of receptor to the recruitment of PI3K as explained above

โ†“

Phosphorylates PIP2 in the membrane

โ†“

Produces PIP3

โ†“

PIP3 serves as a binding site for many proteins e.g, PDK1 (3-phosphoinositide-dependent kinase 1), PKC, or guanine nucleotide exchange factor Vav

โ†“

Different protein has different downstream effect.

For example, PDK1 is seen downstream of insulin receptor

โ†“

Activates Akt (PKB)

โ†“

Akt inhibits glycogen synthase kinase 3-ฮฒ

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โ–ถ๏ธ Tyrosine Kinase Associated Receptor and JAK STAT Pathway
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