Intracellular Signalling 1 Flashcards
What are the different signalling systems between cells?
Inter-cellular - Signalling cell’s surface ligand interacts with receptor on neighbouring target cell
Paracrine - Signalling cell release a local mediator that binds to a receptor on the target cell
Neuronal - Signalling cell is a neuron, which release neurotransmitter across the synaptic cleft and binds to receptor on the target cell
Endocrine - Signalling cell release a hormone that travels in the circulation and binds to a receptor on the target cell in a distal location
What is the role of the adapter protein in the intracellular signalling cascade?
It is often intimately associated with the receptor, such as in the case of GPCRs.
It functions to link the extracellular activation of the receptor to the inside of the cell by activation of the second messenger generator.
E.g G-proteins, Insulin receptor substrates, Shc, Grb
How is it possible that the same ligand/primary messenger can elicit different biological responses in different tissues?
Ligand receptors may exist as different subtypes (isoforms) in different tissues.
The same receptors, when activated, may also initiate different signalling pathways inside the cell.
Single output from different signals or multiple outputs from a single signal
cAMP, IP3/DAG, Ca2+, cGMP, NO and PIP3 are examples of what component in a signalling pathway?
Second messengers
What enzyme generates the second messenger cAMP?
Adenylate cyclase
How does cAMP activate cAMP-dependent protein kinase A?
cAMP binds to regulatory subunits on protein kinase A, causing them to dissociate from the catalytic subunits thus activating the kinase.
What is the function of PLC (Phospholipase C)?
It cleaves a phosphate bond in PIP2 to form membrane-bound DAG and cytosolic IP3.
What is the function of IP3?
Interacts with IP3 receptors on the ER to release intracellular store of Ca2+. Ca2+ activates PKC.
PKC translocates to the plasma membrane where it becomes activated by DAG.
What are some of the functional roles of Ca2+
Can bind to the calcium binding protein calmodulin to activate calcium-dependent protein kinases e.g CaM Kinases
Ca2+ can cause muscle contraction
Ca2+ can influence gene expression
Other than G-protein stimulation, how else can Guanylate cyclase be activated?
By Nitric Oxide - produced from Arginine by Nitric Oxide Synthase.
How it the second messenger PIP-3 produced?
PI3K (Phosphotidyl Inositol 3-Kinase) with ATP converts PIP2 to PIP3.
Name the different ways of signal termination.
Removal of signal/dissociation of ligand from receptor.
Internalisation/degradation of ligand-receptor complex.
Down regulation of receptor expression.
Removal of second messengers: phosphodiesterase, Ca2+ efflux/storage.
Dephosphorylation of activated proteins by phosphatase enzymes.
