CELL SIGNALLING Flashcards
What are the 4 forms of intracellular signalling?
Contact-dependent
Paracrine
Endocrine
Synaptic
In most cells, signal deprivation results in_________.
Apoptosis
What are some causes of different responses to a ligand?
Different receptor proteins (not common).
Differences in intracellular signalling pathways eg activation of intracellular signalling proteins, effector proteins and gene activation.
Describe Intracellular receptors, and the hormone-receptor complex.
Bind lipid-soluble hormones
May be cytoplasmic or nuclear.
Hormone-receptor complex binds to DNA in nucleus, activates genes, initiates transcription and alters protein synthesis.
Slow acting process with a long-lasting effect.
Describe cell surface receptors.
Includes ion channels, GPCRs and enzyme-linked receptors.
Have a faster response and alter protein function.
Describe the role of “second messengers”.
Pass on intracellular signal from receptor to other signalling proteins by binding or altering signalling effector proteins.
Examples include cAMP, calcium ions and diacylglycerol.
Describe the role of intracellular signalling proteins.
Create a functional network to process a signal. Roles include:
Simple signal relay
Signal transformation or transduction
Signal amplification
integration of signals from different pathways
spread signal to another pathway
Anchors proteins to a structure
Describe protein phosphorylation
Transfer of phosphate group to protein substrate.
Acts as a molecular switch for protein activation/inactivation.
Increases or decreases interaction with other proteins (e.g. enzyme substrates, membrane proteins, transcription factors etc).
May cause changes in sub cellular location e.g. migration from cytoplasm to nucleus.
Describe GPCRs.
Largest family of cell surface receptors.
7-pass transmembrane proteins.
Interact with G-protein.
G-protein activation –> activation of target protein (either enzyme or ion channel).
Describe how cAMP is activated by GPCR
- Signal molecule binds to GPCR –> activation or G protein.
- G protein activates adenylyl cyclase, an amplifier enzyme (effector).
- Adenylyl cyclase converts ATP to cAMP (2nd messenger)
- cAMP activates PKA.
- PKA phosphorylates other proteins to amplify the cell signal, leading ultimately to a cellular response.
give 3 examples of GPCRs.
B-adrenergic receptors, glutamate receptors and D2 receptors
Describe Enzyme-coupled receptors.
Activated through ligand binding.
May possess intrinsic enzyme activity or be directly associated with protein catalytic activity (e.g. kinase or phosphatase)
Describe receptor tyrosine kinase activation.
RTKs are present in cell membrane as inactive monomers.
Activation requires dimerisation:
-2 signal molecules –> formation of receptor dimers –> activation of intrinsic TK activity –> autophosphorylation on Tyr –> specific relay proteins activated –> response
Ligands tend to be involved in control of growth and differentiation (e.g. growth factors, cytokines etc)
Describe insulin receptor signalling.
Insulin receptor is a tetrameric protein tyrosine kinase.
Binding of insulin to receptor –>
1. conformational change
2. Activation of intrinsic tyrosine kinase activity
3. Autophosphorylation of Tyr residues
4. activation of insulin receptor substrates (effector proteins) which are cell/tissue specific.
3 major signalling pathways together coordinate regulation of GLUT-4 vesicle trafficking, enzyme activity and gene expression/protein synthesis (glycogen/lipids/protein synth)
What are the 3 major insulin signalling pathways?
PI-3K pathway: metabolic functions
MAP kinase pathway: cell growth
Cbl Pathway: glucose transport
