The Ras Raf Mek Erk Pathway (MAPK)

What is Ras?

A membrane-bound, monomeric GTPase which upon association with SOS, exchanges a bound GDP with a GTP and is activated.

What is the second step in the MAPK pathway, that occurs after autophosphorylation?

Association of GRB2 (growth factor receptor binding protein 2).

What is the third step, after association of GRB2?

Association of SOS.

The is the first response of the receptor upon ligand binding?

Autophosphorylation of tyrosine residues of intracellular regions of the receptor.

Which receptors are linked to the MAPK pathway?

Growth factor receptors such as EGF, PDGF, VEGF etc.

What is the function of Ras?

It binds to and activates Raf kinase.

What is the function of SOS?

It binds to and activates membrane-associated Ras.

What is the function of MEK (MAPKK)?

It phosphorylates ERK (MAPK).

What is the function of MNK?

It phosphorylates and activates CREB: a transcription factor which activates genes involved in proliferation and differentiation.

What is the function of Raf kinase (MAPKKK)?

It phosphorylates and activates MEK (MAPKK).

Which transcription factor is directly activated by MAPK?

MYC.

Which other transcription factors are activated by ERK phosphorylation?

Members of the AP-1 family such as fos/jun.

What is the function of ERK (MAPK)?

Phosphorylates MNK, RSK and MYC.

What is the mechanism of action of fos/jun?

Upon phophorylation, fos/jun translocates to the nucleus and binds to AP-1 promoter motifs, upregulating transcription of genes such as cyclin, growth factors and cytokines. This causes progression of the cell cycle.