Figure 17–64 Stimulation of cell growth by extracellular growth factors and nutrients. The occupation of cell-surface receptors by growth factors leads to the activation of pI 3-kinase, which promotes protein synthesis through a complex signaling pathway that leads to the activation of the protein kinase TOR; extracellular nutrients such as amino acids also help activate TOR. TOR phosphorylates multiple proteins to stimulate protein synthesis, as shown; it also inhibits protein degradation (not shown). growth factors also stimulate increased production of the transcription regulatory protein myc (not shown),  which activates the transcription of various genes that promote cell metabolism and growth. 4E-Bp is an inhibitor  of the translation initiation factor eIF4E. pI(4,5)p2, phosphatidylinositol 4,5-bisphosphate; pI(3,4,5)p3, phosphatidylinositol 3,4,5-trisphosphate.
Figure 17–65 Potential mechanisms for coordinating cell growth and division. In proliferating cells, cell size is maintained by mechanisms that coordinate rates of cell division and cell growth. numerous alternative coupling mechanisms are thought to exist, and different cell types appear to employ different combinations of these mechanisms. (a) In many cell types—particularly yeast—the rate of cell division is governed by the rate of cell growth, so that division occurs only when growth rate achieves some minimal threshold; in yeasts, it is mainly the levels of extracellular nutrients that regulate the rate of cell growth and thereby the rate of cell division. (B) In some animal cell types, growth and division can each be controlled by separate extracellular factors (growth factors and mitogens, respectively), and cell size depends on the relative levels of the two types of factors.
(C) some extracellular factors can stimulate both cell growth and cell division by simultaneously activating signaling pathways that promote growth and other pathways that promote cell-cycle progression.
For proliferating cells to maintain a constant size, they must coordinate their • progression through the cell cycle growth with cell division to ensure that cell size doubles with each division: if cells depends on the phosphorylation grow too slowly, they will get smaller with each division, and if they grow too fast, of hundreds of different proteins by they will get larger with each division. It is not clear how cells achieve this coordi cyclin–Cdk complexes. What are the nation, but it is likely to involve multiple mechanisms that vary in different organ- isms and even in different cell types of the same organism (Figure 17–65).
these proteins are phosphorylated at Animal cell growth and division are not always coordinated, however. In many precisely the right time and place? cases, they are completely uncoupled to allow growth without division or division without growth. Muscle cells and nerve cells, for example, can grow dramatically • during s phase, how are histones after they have permanently withdrawn from the cell cycle. Similarly, the eggs of and their modifying enzymes many animals grow to an extremely large size without dividing; after fertilization, controlled to replicate chromatin however, this relationship is reversed, and many rounds of division occur without structure on the duplicated dna? growth. Compared to cell division, there has been surprisingly little study of how cell • What is the structural basis of size is controlled in animals. As a result, it remains a mystery how cell size is deter-chromosome condensation, and how is the process stimulated during mined and why different cell types in the same animal grow to be so different in mitosis?
size. One of the best-understood cases in mammals is the adult sympathetic neuron, which has permanently withdrawn from the cell cycle. Its size depends on the • What are the mechanisms by which amount of nerve growth factor (NGF) secreted by the target cells it innervates; the greater the amount of NGF the neuron has access to, the larger it becomes. It seems are sensed at the kinetochore by the likely that the genes a cell expresses set limits on the size it can be, while extracel components of the spindle assembly lular signal molecules and nutrients regulate the size within these limits. The chal checkpoint?