Épidermique growth factor

The épidermique growth factor (EGF, of English epidermal growth Factor ) is a proteinic Hormone with the multiple actions, mainly trophic. Its site of action does not summarize with the épidermique fabric but rather with the whole of the fabric S; the épidermique adjective is historical. The fixing of this hormone on the Récepteur with the EGF causes a mitotic activity very fast within targeted fabrics.

Active form

The EGF is synthesized in the form of precursor of 1217 amino-acid then is cleaved to give the mature shape of 53 amino-acids (amino-acid 977 to 1029), which corresponds to a molecular mass of 6,4 kDa. The active form accounts for approximately 4% of the mass of the precursor. The presence of three bridges disulfides increases considerably the stability of the EGF like its resistance to degradation by the Protéase S, while forcing the structure to adopt a rigid conformation.

Transduction of the signal

The EGF is a soluble protein, thus not being able to cross the plasmic membrane Hydrophobe. The transmission of information inside the cell is made by fixing with the receiving specific of the EGF. This fixing induces a dimerisation receiver. There is then trans Phosphorylation on the level of certain residues Tyrosine S of the receiver (activity intrinsic Tyrosine kinase of the receiver). Phosphorylées tyrosins are used as point of anchoring or dockage with proteins with field SH2 ( SRC homolgy domain ) and allow the interaction with other proteins.

4 principal proteins of this type bind to the receiver:
- PLCγ (Phospholipase C gamma)
- GRB2
- GAP (GTPase Activating Protein)
- SRC (protein of the Sarcome the russet-red one)

The phospholipase catalyzes reaction PIP2 (Phosphatidylinositol biphosphate) --> IP3 (Inositol triphosphate) + DAG (Diacylglycérol).
The IP3 joins a ionic Canal endoplasmic Réticulum what causes the release of the ion calcium.
The DAG activates a Protéine kinase of the type C (PKC, protein serine thréonine kinase depending on calcium and phospholipide), insufficiently activated by the basal calcium rate (100 nano mole S per liter).

GRB2 has a field SH3 which recruits factor RAS-GEF ( GDP exchanges Factor ), replacing the GDP of a protein G of the CLOSE-CROPPED type by a GTP. RAS-GTP can then recruit a protein RAF on the level of the membrane, which is phosphorylée by PKC (the reaction is catalyzed by SRC).

RAF phosphoryl goes then phosphoryler and to activate a MAP ( Mitogen Activated ) kinase kinase which will activate a MAP in its turn kinase. The latter phosphoryl factors of transcription JUN and TCF which respectively will cause the expression of oncogenes JUN and FOS.

This way thus leads mainly to an increase in the activity of transcription of the cell and to an increase in the Réplication of the DNA, which results in a stimulation of the cell multiplication and division (Mitose).

Effects biological

Importance in human health

EGF is a molecule which with proteins EGF-like binds on a receiver of the type EGF which is to him a proto-oncogene, i.e. it can be integrated a viral ARN and make so that not only the cell host takes part in the replication of the virus as it is the case for all the viruses but which in more the host cell is it also transformed and becomes a cancerous cell , in which the receiver with the EGF will not have more its normal functioning and will take part in the cellular multiplication. In the case of the receiver with the EGF this one in an abnormal cell will be surexprimé or then there will be changes activatrices, leading in all the cases to a cellular proliferation because of the cascade of reaction described above.

See too

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