LIGANDS and RECEPTORS Flashcards
Necessary for growth, migration, and differentiation of cells in the embryo and their tissue organisation.
Cell Communication
How does Cellular Interactions proceed?
in Multiple Steps.
• 1. Production of signalling molecule.
• 2. Activation of the receptor.
• 3. Biochemical changes resulting in signal
transduction.
• 4. Signal sent to nucleus to affect gene expression (in many cases).
Growth Factors/hormones classifaction
Autocrine
Paracrine
Endocrine
Synaptic
Juxtacrine
Autocrine- Same cell. Paracrine- Close proximity. Endocrine- At a distance. Synaptic- Specific to nerve cells. Juxtacrine- Direct contact.
Combinatorial Signalling
Cells are exposed to many
ligands.
Cells must only respond to some of them.
Most cells must depend on a set of ligands to avoid programmed cell death.
Ligands concentration and affinity
Ligands act at low concentration and they are recognised by their receptor with high affinity.
Do ligands have only one response?
No,
The same ligand can induce different responses in different cells.
– The ligand bind to different receptors.
– The same receptor elicit different responses.
Hydrophilic ligands
can’t cross through membrane) have transmembrane receptors
Small liposoluble ligands
have to cross the membrane to reach an intracellular receptor.
Receptors for Liposoluble Steroid Hormones
Inside the cell they bind to intracellular receptors and activate them
diffuse through cell membrane of target cells to act directly on gene expression
Ligands That Bind to Cell Surface Receptors Are
Hydrophilic
cant not pass through membrane
neurotransmitters
can not pass through membrane
small
growth factors
most are small proteins
- 6-20 kDa in size
some are large
- 90 kDa
3 Receptors for Hydrophilic Water Soluble ligands
Ion Channel Linked, G protein linked, Enzyme Linked
Ion Channel Linked
Ligand open or close ion channel. Involved rapid synaptic signaling.
G Protein Linked
se trimeric G protein as an intermediate to regulate activity of another membrane bound molecule.
Enzyme Linked
Have enzymatic activity or are associated with enzymes when activated
4 classes of enzyme coupled receptors
- Receptor tyrosine kinases
- Receptor tyrosine kinase associated receptors
- Receptor serine/threonine kinases
- Receptor tyrosine phosphatases
3 domains in receptor tyrosine kinases:
- Extracellular domain: large and glycosylated, binds to the growth factor.
- Transmembrane domain: short and composed of hydrophobic amino acids.
- Intracellular domain: contains the catalytic kinase domain.
How Does the Binding of a Protein to the Extracellular Portion of a Receptor Tyrosine Kinase Regulate the Catalytic
Domain on the Other Side of the Protein?
- Growth factor binding cause receptor tyrosine kinase dimerization.
- Dimerization causes transphosphorylation of receptors.
- Phosphotyrosines act as docking sites for SH2 containing proteins.
- Some of those are themselves
phosphorylated by the receptor.
SH2 and SH3 Domains
Small Protein Modules
Their Function Is to Recognise Specific Amino Acids in Their
Target Proteins.
- SH2 and SH3 composed of approximately 100 and 50 aa respectively.
- SH2 and SH3 are Src homology regions 2 and 3.
They are usually shared by the various intracellular substrates of RTKs
Substrates for Receptor Tyrosine Kinases Contain
SH2 Domains and Recognise Phosphotyrosine Residues
Those proteins do not bind to an inactive receptor.
• Some have enzymatic activity.
• Others only act to recruit other signaling molecules.
The Phosphorylation Sites of a Receptor Will Determine
Which Substrates Bind
What residues in a receptor are phosphorylated? What does it create?
specific tyrosine
They creates binding sites for specific substrates
The specificity of the receptor to activate signaling pathways is
built into its primary sequence
