L3 Flashcards
What are the two main mechanisms in cellular responses?
regulation of cytoplasmic activities & changes in gene expn.
Why do we have different cell responses?
differences in protein composition of different cell types
signals affect cell function at multiple levels in ____ and ______
time and space
How do cell signals affect gene expression
TF activation & impact on protein synthesis
How do cell signals affect protein activity
post trns. modification and release from inhibitor
How do cell signals affect cytoskeletal arranagement
Receptor interacts with cytoskeletal proteins which = changes in cell shape and movement.
What is the final effector and what can it lead to
TF (transcription) lead to change in protein expression/synthesis
Are cellular responses linear?
No
What are the three different types of way s signalling pathways can co-operate with each other
convergence, divergence, cross-talk
What do shared transducer molecules enable?
interactions between pathways, coordinated and fine-tuned response
What occurs during divergence?
Different effectors are activated
What does divergence lead to?
Diverse cellular responses
What are the two forms of divergence?
1 pathways can branch = 2 diff cell responses ORsame ligand results in diff reactions in diff cell types
Give an example of the same ligand binding to diff receptors & triggering diff responses
Actylcholine and its effects in skeletal vs heart muscles. In nicotinic receptors present in skeletal muscles, there is an increase in muscle contraction whereas in heart muscles, muscarinic receptors are present, inhibiting muscle contraction.
What occurs during convergence?
2 pathways trigger the same response OR 2 pathways required to activate one cell response
Give an example of convergence seen in cells
Signals converging on Ras = transmitted along MAP kinase cascade.
What are the three receptors that transmit signal re: MAP?
GPCR, receptor kinase, integrin
What is an integrin
transmembrane receptor that anchor cells to extra-cellular matrix; mediates cellular signals such as regulation of the cell cycle, organisation of the intracellular cytoskeleton
What occurs during cross talk?
Signals are passed back and forth between different pathways
Give an example of cross–talk?
MAP kinase and cAMP
MAP = prolif. _ P = CREBP txn factor ACTIVATED
cAMP = blocks signals from Ras -> Raf = inhibiting signals from MAP kinase AND activate CREB txn factor by phosphorylation ?
Why do we try to understand the interactions between pathways?
attempt to pharmacologically inhibit a pathway may be affected by these interactions thus affecting the impact of a therapeutic drug
Are signalling pathways linear?
No
What are signalling networks?
diff signalling pathways interacting through highly connected shared molecules
signals propagate along …
molecular interaction paths
Signalling proteins within networks act as modules that integrate & distribute regulatory information to
respond to multiple signal inputs
regulate multiple effector outputs (cell responses)
What is the data processing network of the cell based on?
chemical interactions and cross talks
What is systems biology?
understanding overall architecture of the signalling network, need to identify interactions between connected proteins
What are things used in systems biology
experimental data & computational stimulation and mathematical models
What are the different areas of biology studied when looking at signalling networks?
Genomics, Transcriptomics, Proteomics, Metabolomics
What are the advantages of using systems biology?
Signalling networks help biologists understand interactions between proteins
Explain why some drugs can affect multiple pathways- could be used to design new drugs
What are the possible issues with systems biology?
complexity and flexibility of such networks prevents a more in-depth analysis of their physiological functions
What are the factors impacting the signalling pathways of diseases?
Genetics factors, environmental and lifestyle factors
What is carcinogenesis
multi-steps process; accumulation of genetic mutations leads to acquisition of tumour phenotype
How many mutations normally for cancer?
6-7 mutations
What are the cancer prevention mechanisms?
Antioxidant mechanisms, tumour suppressor genes, repair mechanisms and immunoserveillance
What are cancer hallmarks?
- grow and divide in absence of signal
- evade growth suppressors
- resist apoptotic signals
and can potentially induce angiogenesis as well as invasion and metastasis at later stages to allow the cancer to spread too other parts of the body
What is underlying the hallmarks of cancer?
genetic instability and inflammation
What is the approach used in the therapeutic targeting of the hallmarks of cancer
drugs that target signalling pathways
What are the types of signal transduction in cancer cells?
Mutations in genes coding for
signal transducing protein (e.g. Ras, small G protein)
Tumour suppressor (TP53) and oncogenes (cMYC)
Growth factor receptors
inhibitors of proliferation
Growth factors:
switch from paracrine to autocrine signalling
Alteration in pathways controlling
cell division, apoptosis, angiogenesis, inflammation, immune function, DNA repair…
What occurs in T1 diabetes?
cells fail to produce signal - autoimmune targeting of pancreatic Beta cells
What occurs in T2 diabetes?
cells fail to respond to signals
What does diabetes lead to?
High blood glucose levels
