High resolution

Module 9: Figure G1 proliferative signalling

Spatiotemporal aspect of proliferative signalling.

Competence growth factors initiate a number of signalling pathways that carry information into the nucleus to activate immediate early genes. Some of these early genes encode information for the expression of progression growth factors (GFs) and their receptors (GFRs) to set up an autocrine loop to drive later events. Other early genes encode transcription factors such as E twenty-six (ETS), Jun and Myc to initiate transcription of later genes, such as cyclin D, which combines with the cyclin-dependent kinases (CDKs) to phosphorylate the retinoblastoma protein (Rb): one of the key gate-keepers guarding passage through the restriction point (R). A key event at the restriction point (R) is the phosphorylation of Rb, which removes its inhibition of E2F and enables this transcription factor to increase the expression of the cell cycle components (e.g. cyclin E, cyclin A and Cdc25A) responsible for initiating DNA synthesis. Further details of this activation sequence are provided in Module 9: Figure cell cycle signalling mechanisms.