PAUSE - LIGANS AND RECEPTORS

Question 1

what is cell communication necessary for?

Answer 1

growth, migration, and differentiation of cells in the embryo and their tissue organisation

Question 2

what can defects in cell communication cause?

Answer 2

cancer, diabetes, disorders of the immune and cardiovascular system

Question 3

what are the multiple steps in cellular interactions?

Answer 3

1. production of a signalling molecule
2. activation of the receptor
3. biochemical changes resulting in signal transduction
4. signal sent to nucleus to affect gene expression

Question 4

what are the different distances that ligands act at and the names for that?

Answer 4

autocrine: same cell
paracrine: close proximity
endocrine: at a distance
synaptic: specific to nerve cells
juxtacrine: direct contact

Question 5

how can ligand induce different responses in different target cells?

Answer 5

same ligand can induce different responses in different cells
ligand binds to different receptors
same receptors elicit different responses

Question 6

how do ligands act?

Answer 6

at low concentration
and recognised by their receptors with high affinity

Question 7

what do hydrophilic ligands recognised?

Answer 7

transmembrane receptors

Question 8

how are liposoluble ligands recognised?

Answer 8

have to cross the membrane to reach an intracellular receptor and activate it

Question 9

what are the sizes of the different ligands?

Answer 9

frequently small molecules
most are factors are small proteins (peptides) 6-20kDa In size
some growth factors are large proteins

Question 10

what are the three classes of cell surface receptors?

Answer 10

Ion Channel linked: ligand open or close ion channel, involved rapid synaptic signaling
G protein linked: use 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

Question 11

what are the four classes of enzyme coupled receptors?

Answer 11

1. receptor tyrosine kinases
2. receptor tyrosine kinase associated receptors
3. receptor serine/threonine kinases
4. receptor tyrosine phosphatases

Question 12

what are the three domains and their characteristics in receptor tyrosine kinases?

Answer 12

1. extracellular domain: large and glycosylated, binds to the growth factor
2. transmembrane domain: short and composed of hydrophobic amino acids
3. intracellular domain: contains the catalytic kinase domain

Question 13

how are receptor tyrosine kinases activated by a ligand?

Answer 13

1. Growth factor binding cause receptor tyrosine kinase dimerization.
2. Dimerization causes transphosphorylation of receptors.
3. Phosphotyrosines act as docking sites for SH2 containing proteins.
4. Some of those are themselves
   phosphorylated by the receptor.
5. can now bind to signalling proteins

Question 14

what are the characteristics of SH2 and SH3 domains?

Answer 14

composed of approximately 100 and 50 aa respectively
SH2 and SH3 are Src homology regions 2 and 3
usually shared by various intracellular substrates of RTKs (which have diverse structure and functions)

Question 15

how is specificity of the receptor set up?

Answer 15

phosphorylation site of a receptor determines which substrates bind
only specific tyrosine residues are phosphorylated
create binding sites for specific substrate
not al receptors have the same substrates
specific is built into primary sequence