Lecture 6- cell signalling Flashcards
Learning Outcomes
Communication betweencells
*Describe and explain the types of communication between cells
*Compare and contrast the response times for the different signals
*Discuss the impact of the signal at a local and whole organism level
Receptor types:
*Discuss the longevity and impact of the changes to the cell in response to activation of the different receptor types.
Experimental Applications:
*Detection of calcium ion concentration
Principles of signalling:
For any signal to be received or sent you need the following:
◦The signal itself -can be protein, short peptide, ion, small molecule e.g. nucleic acid.
◦A means of the signal getting to its desired destination e.g. systemic circulation
◦Something to receive the signal -a receptor e.g. a tyrosine kinase receptor such as insulin receptor.
◦Something that can interpret the signal -second messengers such as kinases.
◦A response to the signal -the outcome for the cell e.g. transcription of particular genes or changes in enzyme activity.
Think of examples of signalling pathways
Signaling pathways are complex networks of proteins and molecules that transmit signals from outside a cell to its interior, leading to a specific cellular response. Here are some key examples of signaling pathways:
- Receptor Tyrosine Kinase (RTK) Pathway
Example: Epidermal Growth Factor Receptor (EGFR) Pathway
Function: Upon binding of epidermal growth factor (EGF) to EGFR, the receptor dimerizes and undergoes autophosphorylation. This activates downstream signaling pathways, including the MAPK/ERK pathway and the PI3K/AKT pathway, leading to cell proliferation, survival, and differentiation. - G Protein-Coupled Receptor (GPCR) Pathway
Example: Adrenergic Receptor Pathway
Function: When adrenaline binds to adrenergic receptors, it activates G proteins that trigger a cascade of intracellular events. This can lead to increased heart rate, glycogen breakdown, and mobilization of energy. - Mitogen-Activated Protein Kinase (MAPK) Pathway
Example: ERK Pathway
Function: This pathway is activated by various growth factors and leads to cell growth, differentiation, and survival. It typically involves a cascade of phosphorylation events, with the activation of MAPK kinases (MEK) and then MAPKs (like ERK), ultimately affecting gene expression. - Transforming Growth Factor Beta (TGF-β) Pathway
Function: TGF-β binds to its receptors and activates SMAD proteins. Once phosphorylated, SMAD proteins translocate to the nucleus, where they regulate the transcription of target genes involved in cell growth, differentiation, and immune responses. - Wnt/β-catenin Pathway
Function: In the absence of Wnt ligands, β-catenin is degraded. When Wnt binds to its receptor, β-catenin accumulates and translocates to the nucleus, where it regulates gene expression involved in cell proliferation and differentiation, crucial for development and stem cell maintenance. - Notch Signaling Pathway
Function: Involves the interaction between Notch receptors and their ligands (e.g., Delta). When a ligand binds to Notch, it undergoes cleavage and releases the Notch intracellular domain (NICD), which translocates to the nucleus to regulate target gene expression important for cell fate determination. - JAK-STAT Pathway
Function: Cytokine receptors activate Janus kinases (JAKs) upon cytokine binding. JAKs phosphorylate Signal Transducers and Activators of Transcription (STATs), which then dimerize and translocate to the nucleus to modulate gene expression involved in immune responses and cell growth. - Nuclear Factor kappa B (NF-κB) Pathway
Function: NF-κB is typically sequestered in the cytoplasm by IκB proteins. Upon stimulation (e.g., by cytokines), IκB is degraded, allowing NF-κB to translocate to the nucleus and regulate genes involved in inflammation, immune response, and cell survival. - PI3K/AKT Pathway
Function: Activated by growth factors binding to RTKs or GPCRs, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to produce phosphatidylinositol 3,4,5-trisphosphate (PIP3). This activates AKT, which promotes cell survival and growth by inhibiting apoptosis and promoting metabolism. - cAMP Pathway
Example: Beta-Adrenergic Signaling
Function: GPCRs activate adenylate cyclase to convert ATP to cyclic AMP (cAMP), which activates protein kinase A (PKA). This pathway regulates various physiological processes, including glycogen breakdown and lipolysis.
Conclusion
These signaling pathways play critical roles in regulating numerous cellular functions, including growth, differentiation, metabolism, and apoptosis. Dysregulation of these pathways can lead to various diseases, including cancer, diabetes, and cardiovascular disorders. Understanding these pathways is essential for developing targeted therapies and treatments.
There are four basic mechanisms for cellular communication
a.Contact-dependent (directcontact)
b.Paracrinesignaling
c.Synapticsignaling
d.Endocrinesignaling
Cell Communication
Cell’s behaviour depends on multiple extracellular signal molecules. Each cell displays a set of receptors allowing it to be stimulated by a set of ligands produced by other cells. These molecules work in synergy to regulate the cell’s behaviour.
Contact-dependent Cell Communication
Contact-dependent –molecules on the surface of one cell are recognized by receptors on the adjacent cell
Paracrine signalling
Paracrine signalling –signal released from a cell has an effect on neighbouring cells
Paracrine signalling –Examples
Fibroblast growth factor (FGF) –Proliferation and differentiation Transforming growth factor beta (TGFβ) –Growth, differentiation, proliferation and apoptosis Wnt signalling –embryo development
IL6, Wnt and vascular endothelial growth factor also autocrine
Paracrine signalling –Chemotaxis
Chemotaxis-motility in the direction of a localised mediator Bacterial toxins –formyl peptides (tetrapeptides) Chemokines –IL8
Synaptic signalling
Synaptic signalling –nerve cells release the signal (neurotransmitter) which binds to receptors on nearby cells
Cholinergic transmission
Endocrine signalling
Endocrine signalling –hormones released from a cell affect other cells throughout the body
Speed of transmission
Extracellular signals can act slowly (e.g. growth and cell division) or rapidly (e.g. cell movement) to change the behavior of a target cell.
Cell Communication depending on the cell
Different cell types will respond differently to the same extracellular signal molecule.
Method of interpretation: second messengers
Proteins (including enzymes) are modified Modification changes shape or charge of molecule including (but not limited to):
➢Phosphorylation
➢Acetylation
➢Methylation
➢Cleavage
Changes enable either the activation of enzymatic function or recognition by another protein.
Signal transduction: Phosphorylation
Protein kinases and phosphatases are employed in virtually all signaling pathways
Signal transduction: GTPases
GTP-binding proteins are often used in signal transduction as on/off switches
GDP is bound to the GTPase, which has no activity.When associated with the GEF, GDP is removed and GTP is able to bind, causing a shape change and increase in activity.
GAP proteins aid removal of a phosphate group (Pi) from GTP (to generate GDP), rendering the GTPase as inactive again
