L3 - Introduction to cell signalling III Flashcards
How do signals affect cell function?
Gene expression
Activity of cytoplasmic or nuclear protein
Cytoskeletal rearrangement
How do signalling pathways affect gene expression?
By switching ON or OFF the expression of certain genes
So the final activated effector of a signalling pathway – often a transcription factor
The consequences will be to modify protein synthesis
Changes in gene expression are expensive
How do signalling pathways affect activity of cytoplasmic or nuclear protein?
Usually through post-translational modifications, but also through release of an inhibitor (eg. NFkB or IkB)
How do signalling pathways affect cytoskeletal rearrangement?
Some cell receptors directly interact with cytoskeletal proteins & induce, upon ligand-binding, changes in cytoskeletal organisation (eg. integrins receptors can affect cell adhesion to extracellular matrix)
Or signalling molecules (eg. by small GTPase protein Rho) can affect actin cytoskeleton resulting in changes in cell shape & movement, in response to growth factors, cytokines & hormones
Receptors & transcription factors
Transcription factors can be directly activated by phosphorylation (through a kinase) at the receptor
Transcription factors migrate into the nucleus from the cytosol
Altered gene expression:
• Final effector is usually a TF
• Turn ON or OFF gene expression
• Can lead to a change in protein expression
Relationship between signalling pathways
Each cell expresses dozens of different receptors sending signals to the inside of the cell simultaneously
These signals are transduced & integrated along the different pathways inside the cell
Shared transducer molecules between different molecular pathways:
• Enable interactions between pathways
• Enable cells to prove a coordinated response
• Ensure a fine-tuning of the response
How do signalling pathways co-operate with each other?
Convergence
Divergence
Cross talk
DIVERGENCE
1 ligand can trigger multiple responses
Same ligand sends signals along a variety of different pathways & activates different effectors leading to a diverse cellular response
Same ligand can bind to different receptors & trigger different reposnes in different cell types
CONVERGENCE
May be regulated or depends on activation of multiple pathways
2 pathways may trigger the same response, or 2 pathways may be required for the activation of 1 cell response
Mitogen-activated protein (MAP) kinases – represent a point of convergence for cell surface signals regulating cell growth & division
CROSS TALK
Can modulate other cell response
Signals are passed back & forth between different pathways
Eg. Cross-talk between cAMP signalling & MAP kinase signalling cascades:
Problems with signalling pathways co-operating with each other?
Attempts to pharmacologically inhibit a pathway are made difficult this affecting the impact of a therapeutic drug
What are signalling networks?
Are formed of different cell signalling pathways that interact though highly connected shared molecules
Instead of activating a simple sequence of events, 1 signal activates a network of highly connected signalling proteins that process the signal to produce a coordinated response
What is cancer?
Cancer is a multi-step process during which cells acquire tumour phenotype through the accumulation of genetic mutations
However, some inherited cancers don’t need an accumulation of mutations
Mutations causing cancerous phenotypes generally…
Enable expansion of tumour clone
Increase mutation rate
Enable invasion & migration
Early features of cancer cells
Grow & divide in the absence of a signal
Evade growth suppressors
Resist apoptotic signals
