Adjusting Cellular Sensitivity
Number of Transducers
Number of Receptors
Spare Receptors - Multiple Hypotheses
Cell has 2 pools, 1 "true" or active, 1 "spare" or inactive
"Spare" R only reflect those not coupled to the response being monitored
Spare R [R] [H] + [R] [HR], favors [HR] and responses to HR, allows
regulation without altering Ka
Location of Receptors
Expression on part of the cell surface regulates exposure
may allow directional or polar responses to hormone
Biochemical Status of Receptors
Receptor aggregation alters surface location and may trigger
cellular internalization of HR with proteolysis of H and/or R (receptor
- mediated endocytosis; associated with at least temporary R inactivation
and inaccessibility to H)
Receptor aggregation may trigger tyrosine kinase activities
that alter receptor association with hormone (Ka), other receptors
or with transducers
Transducer/Effector molecules may phosphorylate receptors
and alter receptor associations as in 3b.
Interactions with multiple transducer systems may deplete
Location of Transducers
Intracellular localization of transducers in membranes,
near receptors make them more available than if they must diffuse along
cytoskeletal elements in the cytoplasm; recruitment to one end of the cell
by a highly localized receptor may make them unavailable for coupling to
receptors at the other end of the cell.
Biochemical Status of Transducers
Number of Effectors
Allosteric interactions mediated by binding to GTP/GDP,
ATP, IP3,DAG, or other small molecules may activate or inactivate
Phosphorylation, or other covalent biochemical modifications
may activate or inactivate transducer elements.
As for transducers.
Location of Effectors
Proximity to receptor/transducer elements helps speed
modulations of activity.
Biochemical Status of Effectors
As for transducers, except that availability of suitable
substrates may also alter activity levels and these may be affected by
activities of transducers.