How do growth factors cause cell division?

Growth factors are proteins that regulate various cellular processes, including differentiation and cell division. How do growth factors make cells divide? Simulation of cell division is triggered when particular growth factors bind cell receptors. This triggers a cascade of events through a series of steps that result in mitosis and cell division:

1. Binding to Receptors: Growth factors bind to specific receptors on the surface of target cells. These receptors are typically transmembrane proteins with an extracellular domain that binds the growth factor and an intracellular domain that transmits the signal into the cell.
2. Receptor Activation: The binding of a growth factor to its receptor induces a conformational change in the receptor, leading to its activation. This often involves the dimerization (pairing) of receptor molecules and autophosphorylation (addition of phosphate groups) of specific tyrosine amino acid residues in the intracellular domain.
3. Signal Transduction: Once activated, the receptor initiates a cascade of intracellular signalling pathways. There is a degree of redundancy: Multiple pathways can be activated by a single growth factor and different growth factors can stimulate overlapping pathways. Key pathways involved in cell division include the MAPK/ERK pathway, the PI3K/AKT pathway, and the JAK/STAT pathway. These pathways transmit the signal from the cell membrane rippling through to the nucleus via a series of phosphorylation events and protein-protein interactions.
4. Transcriptional Activation: The signalling pathways ultimately lead to the activation of transcription factors in the nucleus. These transcription factors bind to specific DNA sequences and promote the transcription of genes that are essential for cell cycle progression and division. Examples of such genes include cyclins and cyclin-dependent kinases (CDKs), which are crucial regulators of the cell cycle.
5. Cell Cycle Progression: The proteins produced as a result of transcriptional activation drive the cell through the different phases of the cell cycle. Cyclins and CDKs form complexes that regulate the transition between different phases of the cell cycle, such as the G1 phase (cell growth), S phase (DNA synthesis), G2 phase (preparation for mitosis), and M phase (mitosis or cell division).
6. Cell Division: The cell is still not ready to divide. Along the way, it has to pass through cell cycle checkpoints. These are surveillance mechanisms used by the cell to make sure everything is in good order. For example, the cell needs to have grown to the appropriate size and completed DNA replication. Once these conditions have been satisfied, the cell undergoes mitosis, resulting in the division of the parent cell into two daughter cells. Each daughter cell receives an identical set of chromosomes and can continue to grow and divide in response to growth factors.

Externally administered growth factors either accelerate or are essential for cell division. In tissues, these steadily ramp up and down. Typically cell culture adds growth factors in excess to compensate for degradation. PODS depot growth factors provide a much steadier profile.

IMAGE How growth factors cause cell division CREDIT: Cell Guidance Systems Ltd

Learn more about powerful technologies that are enabling research: