Figure 2.

GPCR transactivation of EGFR leads to the activation of multiple mitogenic pathways. GPCR/G protein activity of many families of G protein promotes the activity of MMPs via PLCβ-dependent, or possibly Src-dependent (indicated by dashed lines – see text for further details), mechanisms. MMP activity releases EGF in its soluble form. The resulting EGFR activity promotes the formation of a signalling complex and the activation of PI3K, MAPK and ROCK kinases in a GPCR and cell type specific manner. The increased expression of cyclins promotes progression into S phase, while the upregulation of CDK inhibitors p21^Cip1 and p27^Kip1 delays S phase entry. Dashed lines also identify the probable involvement of multiple, unidentified intermediates in the transcriptional regulation of cell cycle proteins.