Factors affecting the specificity of hormone action:

1. Cell must possess receptor for hormone in order to respond.
2. Cells have receptors for, and respond to, different hormones, but with similar intracellular responses, e.g., [cAMP]­ ; [Ca²⁺]­ .
3. Different RTKs, upon Tyr phosphorylation, erect different assemblies of heteromultimeric protein complexes and thereby achieve unique responses.

Mitogens are extracellular growth factors (polypeptide hormones) that promote cell division (mitosis). Cancer is a disease arising from uncontrolled cell division. Many of the genes involved in the RTK-based signal transduction cascades activated by mitogens can mutate and become oncogenes: cancer-causing genes. The wild-type (unmutated) forms of these genes that function in regulation of cell division are termed proto-oncogenes.

The gene encoding the protein ras (a small G-protein) is a good example.

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Reproduction of cells: The universal paradigm:

The cell first copies all its genes and then allocates them equally to 2 daughter cells, which are thus genetically equivalent.

Prokaryotes: reproduce by binary fission (Figure 9.3)

Single, circular chromosome attached to plasma membrane at the mesosome (a structural feature recognized as an invagination of the membrane). The chromosome replicates, and the plasma membrane and the cell wall grow between the attachment sites. Cell grows to about twice original size, plasma membrane and cell wall pinch inward, and each daughter cell ‘captures’ a chromosome.

Eukaryotic cells contain many chromosomes (46 (23 pairs) in humans, 94 (47 pairs) in goldfish), each consisting of a DNA-protein complex called chromatin – a very long, thin, coiled fiber.

Cell division involves:

1. chromosome duplication
2. mitosis: distribution of the chromosomes to 2 daughter nuclei
3. cytokinesis: division of cytoplasm to form 2 daughter cells

As times for cell division nears, dispersed chromosomes in the nucleus duplicate and condense to form 2 identical structures called sister chromatids. That is, each chromosome (each consisting of proteins + a linear, double-stranded DNA molecule) replicates, forming 2 identical structures (the sister chromatids, each containing a single, double-stranded DNA molecule), which remain joined together at numerous sites as well as at a specialized region called the centromere.

The process of mitosis distributes 1 of the 2 sister chromatids to each of the daughter nuclei.

In addition to chromosome duplication, most cells also increase in mass and in their supply of organelles before division: ribosomes, ER, etc. partitioned roughly equally.

Mitochondria and chloroplasts: Semi-autonomous replication: mitochondria and chloroplasts have their own DNA, and these organelles replicate somewhat in tune with cell division, so that each can be contributed to the daughter cells.

The Eukaryotic Cell Cycle (Figure 9.4)

An ordered series of events.

In a dividing somatic cell, the M (or mitotic) phase alternates with an interphase (or growth) period.

The M phase consists of mitosis (prophase, metaphase, anaphase, telophase) and cytokinesis.

The interphase consists of:

1. G₁ (Gap 1)
2. S (the period of DNA synthesis)
3. G₂ (Gap 2): the period when the cell prepares to enter M. Mitosis begins at the end of G₂.

Actively dividing cells divide about once every 16-24 hours. (In early embryonic cells, no G₁ and G₂, just S and M; the cells get smaller and smaller.)

In rapidly replicating human cells, the full cell cycle takes about 24 hours:

M takes about 30 minutes; G₁ takes about 9 hours; S takes about 10 hours; and G₂ takes about 4.5 hours.

In rapidly growing yeast cells, the full cell cycle takes only 90 minutes.

Adult human: 10¹⁴ cells

Neurons, RBC, skeletal-muscle cells : have lost the ability to divide.

Liver cells: retain potential to divide if necessary.

Epithelial cells: divide continuously and rapidly.

Differences in cell cycle times are differences in G₁, or more appropriately, differences in G₀.

G₀: Postmitotic cells in multicellular organisms can ‘exit’ the cell cycle and enter G₀: a non-proliferative state that can last days, weeks, or, in some cases (nerve cells, cells of the eye lens) for the lifetime of the organism. The cells of most vertebrates exit G₁ and enter G₀ for substantial periods. Entry into and exit from G₀ is tightly regulated, thus providing control over cell proliferation.

Cell division is initiated by both internal and external signals (such as mitogens). Errors in these signals cause cells to divide inappropriately and form a disorganized mass of cells (tumor).

Once a cell leaves G₁ and enters S, it is committed to divide. The point of no return is called the restriction point (R, also called start). R occurs late in G₁. Cells that don’t divide arrest cell division at this point, and at this point only. Feedback mechanisms control cell division, signaling a cell to pass R and enter S if, and only if, new cells are needed. Without such control, form & function in multicellular organisms would be quickly lost.

Key aspects: The eukaryotic cell cycle must ensure faithful transmission of the genome.

1. DNA replication: Chromosomes must be duplicated once, and only once, per cell cycle.
2. Chromosome segregation: separation and equal partitioning of sister chromatids.
3. Exit from the M phase into interphase.

At each stage, there are surveillance mechanisms (checkpoints) to ensure that previous events have proceeded correctly. If not, cell division arrests at the checkpoint.