Events of the cell cycle
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The cycle begins late in G1 when the cell passes a restriction point. The cell then proceeds systematically through the S phase (synthesis), G2, and M phase (mitosis).
To respond to a mitogen growth factor, a cell must have the cor- responding receptor on its cell surface. Many cells in the body synthesize and secrete mitogens, which then influence the proliferation of other cell types in a paracrine or endocrine fashion. Platelet-derived growth factor (PDGF) was one of the first mitogens to be discovered. It is secreted by platelets when they form blood clots in response to an injury. PDGF stimulates fibroblasts and smooth muscle cells in the damaged area to divide and replace cells lost to the injury. Numerous mitogens have been identified, and most cells require an appropriate combination of mitogen signals before they can enter the cell cycle. There are many signaling steps in the pathway from mitogen receptor to DNA activation. Somatic cells respond to GFs by increasing cell size, whereas stem cell populations undergo cell division. Thus the same signaling ligands may have different effects depending on cell type and conditions. Similar signaling pathways may also trigger cell death (apoptosis) when cells have to be reduced or removed during tissue development and remodeling. The processes of abnormal cellular proliferation and cancer are further detailed in Chapter 7. The process of apoptosis is described in Chapter 4.
KEY POINTS • Intercellular communication is accomplished by three principal means: (1)
gap junctions, which directly connect the cytoplasm of adjoining cells; (2) direct cell-to-cell surface contact; and (3) secretion of chemical mediators (ligands). Most ligands are water-soluble molecules that interact with receptors on the cell surface. These receptors are of three general types: ion channel linked, enzyme linked, and G-protein coupled.
• Binding of a ligand to a G-protein receptor controls the production of second messengers (cAMP, IP3, DAG, Ca
2+) within the target cell that initiate changes in cell function.
• Somatic cells divide by a process called mitosis in which daughter cells each receive an identical and complete set of 46 chromosomes.
• Cell replication normally requires specific extracellular mitogens that activate signaling systems within the cell. Cyclin proteins and Cdk alter the function of Rb protein, causing it to release transcription factors that begin the process of cell replication.
bind to DNA promoter regions and begin the processes of cell replication. The Rb protein can be induced to release the E2F transcription factors when appropriate mitogen signals arrive at the cell surface. These proliferation-promoting signals at the cell surface are transmitted to pRb by way of cyclin-dependent signaling pathways within the cell. Proteins called cyclins accumulate in the cell and then bind to and activate cyclin-dependent kinases (Cdk). The Cdk then phosphorylates pRb, changing its affinity for E2F so that it is released. The E2F then translocates to specific regions of DNA where it regulates more than 500 genes and promotes cell replication.