Biochemical Messengers Flashcards
Learning Outcomes
- Have an understanding of the various mechanisms cells use
for communication. - Be able to list components of cellular communication:
receptors and signal molecules, intracellular signalling
pathways and messengers, effectors. - Describe the functions of molecular switches
(kinases/GTPases) in signalling - Be able to describe an example of common cell signalling
mechanisms in detail.
How do cells change?
- Gene-protein expression?
→ transcription factors - Enzyme activity?
→ phosphorylation (kinase/phosphatase)
→ association (co-activators/co-repressors) - Secretion?
→ ion channels (Ca2+ trigger)
Extracellular signalling → intracellular signalling
Why do we communicate?
- To convince other people to do what you want
them to do (modify their behaviour = change) - Cells convince other cells too
Communication components
- Synthesis of signalling molecule (1)
- Signal release (2)
* Stimulus → Exocytosis - Transport to target cell (3)
* Endocrine, Paracrine, Autocrine, Plasma-membrane attached
proteins (Juxtacrine) - Bind cellular receptor (4)
* Signals only affect target cells with receptors for that signal
(lock and key) - Respond to signal (5,6)
* Receptor conformational change launches a series of
biochemical reactions within the cell called signal transduction
cascades which amplify the message and relay it to an
EFFECTOR protein - Effect cell function (7)
* Molecular switches activate effector proteins (switch on
enzymes, activate transcription factors)
* Effector proteins change cell function - Removal of signal – feedback (8,9)
Benefits & limitations
Long distance
* Slower
* More generalised
* Plasma ligand dilution necessitates high
affinity receptor binding
Extracellular Signalling - distance
Short distance
* Faster
* More precise
* High concentration means low affinity
receptor binding works
Protein/peptide signals
*Vast majority
*Stored in secretory granules or vesicles
→ exocytosis release
*Hydrophilic –bind cell surface receptors
& activate intracellular signalling paths
*Rapid acting, short lived
*Act quickly (minutes of release).
*Rapidly destroyed (minutes).
*Inactivation
*Degraded enzymatically.
*Endocytosed.
Extracellular signalling molecules
Hydrophobic signals - steroids
Steroid hormones:
Lipids: derived from cholesterol.
Include: cortisol, aldosterone,
testosterone, oestrogen, progesterone.
Hydrophobic:
- Require transport proteins
- Bind intracellular receptors
Much longer lived
Hydrophobic signals - steroids
Inactivation (Liver)
1. Enzymatically deactivated
(Cytochrome P450 oxidase)
2. Excretion in bile
The same messenger can cause many changes:
e.g. acetylcholine (ACh)
Receptors
Cell-surface Rs vs. Intracellular Rs
Intracellular receptors
- Nuclear receptors are inactivated
transcription factors - Ligand binding causes activation
- Transcription factors regulate
transcription of target genes
(often 1000s, can be +ve or -ve) - Oestragen, testosterone, cortisol, vitA,
vitD, thyroid hormone
Intracellular receptors
Intracellular receptors
2 types of nuclear receptor
Cell-surface receptors: meet the 3 largest classes
Cell-surface receptors: meet the 3 largest classes
Cell-surface receptors: meet the 3 largest classes
Metabotropic cell-surface receptors relay
signals via intracellular signaling molecules
RTKs - Kinase switch activates signal proteins
GPCRs activate G-proteins
GPCRs activate G-proteins
Second messengers
Receptor activation causes
signalling complexes to
form
Receptor activation causes
signalling complexes to
form
G-proteins/kinases activate 2nd messengers
RTKs and GPCRs activate many signalling pathways
summary
Examples… cAMP activates cAMP-Dependent Protein Kinase (PKA)
Examples… Inositol 1,4,5-triphosphate (IP3
) signaling → Ca2+
release → PKC activation
