WEEK 12 (Cell signalling) Flashcards
What are Chemical messengers?
Chemical messengers transmit messages between cells and are secreted from one cell in response to a specific stimulus and travel to a target cell, where they bind to a specific receptor and elicit a response
What are chemical messengers in the Nervous system, Endocrine system & Immune system?
- Nervous system = Neurotransmitters
- Endocrine system = Hormones
- Immune system = Cytokines
What are the different forms of Chemical signalling?
- Autocrine
- Signalling across gap junctions
- Paracrine
- Endocrine
What are the two types of messengers that the nervous system secretes?
- Small-molecule neurotransmitters (biogenic amines)
- Neuropeptides
What are small-molecule neurotransmitters?
Nitrogen-containing molecules, several of which are amino acids or derivatives of amino acids
What are neuropeptides?
Small peptides, secreted by neurons, that act as neurotransmitters at synaptic junctions or are secreted into the blood to act as neurohormones
What are Endocrine hormones?
Compounds secreted from specific endocrine cells in endocrine glands which reach their target cells following transport through the blood
What are the properties of Water-Soluble hormones?
- Receptor in cell membrane
- Second messengers often involve Protein kinases activated
- Protein phosphorylation to modify activity of enzymes
EXAMPLES:
- Insulin
- Glucagon
- Catecholamines
What are the properties of Lipid-Soluble hormones?
- Receptor inside cell
- Hormone-receptor complex binds to enhancer regions of DNA
- Control of gene expression
EXAMPLES:
- Steroids
- Calcitriol
- Thyroxines
- Retinoic acid
What is the importance of cytokines?
- Small protein messengers of the immune system
- Regulate a number of responses designed to kill invading microorganisms
- Alter behaviour of other cells in the immune system by ACTIVATING THE TRANSCRIPTION OF GENES for proteins involved in the immune response
- CHEMOKINES have the ability to induce movement in targeted cells toward the source of the chemokines
What is the importance of Eicosanoids?
- Control cellular function in response to injury
- Derived from ARACHIDONIC ACID (a 20-carbon polyunsaturated fatty acid present in cells as part of the membrane lipid phosphatidylcholine)
What are examples of Hydrophilic hormones?
- Peptide hormones
- Cytokines
- Catecholamines
[cannot rapidly cross the plasma membrane so must bind to a plasma membrane receptor]
What are examples of Hydrophobic hormones?
- Steroid hormones
- Thyroid hormone
- Retinoic acid
- Vitamin D
[can cross the plasma membrane so can bind to intracellular receptors]
What are the properties of Lipophilic hormones?
- Compounds are water-insoluble so are transported in the blood bound to SERUM ALBUMIN (has a hydrophobic binding pocket), STEROID HORMONE-BINDING GLOBULIN (SHBG) or THYROID HORMONE-BINDING GLOBULIN (TBG)
- Intracellular receptors for these hormones are called STEROID HORMONE/THYROID HORMONE SUPERFAMILY OF RECEPTORS
What do all plasma membrane receptors have in common?
- An extracellular domain that binds the chemical messengers
- One or more membrane-spanning domains that are α-helices
- An intracellular domain that initiates signal transduction
Describe how Plasma membrane receptors function
The ligand binds to the extracellular domain of its receptor -> causes a CONFORMATIONAL CHANGE communicated to the intracellular domain through the rigid α-helix of the TRANSMEMBRANE DOMAIN -> Activated intracellular domain initiates a characteristic SIGNAL TRANSDUCTION PATHWAY that usually involves the binding of specific intracellular signal transduction proteins
What are the effects of signal transduction on the cell?
- RAPID and IMMEDIATE effects on cellular ion levels or activation/inhibition of enzymes
- SLOWER CHANGES in the rate of gene expression for a specific set of proteins
What are the major classes of plasma membrane receptors?
- Ion channel receptors
- Receptors that are kinases/bind to and activate kinases
- Receptors that work through second messengers
What are Ion channel receptors?
Passageways or ion channels that have the ability to open and close in response to chemical or mechanical signals
What are Heptahelical Receptors?
Plasma membrane receptors that contain seven membrane-spanning α-helices that work through first and second messengers
Describe how Heterotrimeric G-proteins function
1) While the α-subunit contains bound GDP, it remains associated with the β and γ subunits, either free in the membrane or bound to an unoccupied receptor
2) When the hormone binds, it causes a CONFORMATIONAL CHANGE in the receptor that promotes GDP dissociation and GTP binding -> exchange causes dissociation of α-subunit from β and γ subunits
3) The GTP α-subunit binds its target enzyme in the membrane, thereby changing its activity
Describe how Kinase receptors function
1) Intracellular kinase domain of the receptor is activated when the messenger binds to the extracellular domain
2) Receptor kinase phosphorylates an amino acid residue on the receptor and/or an associated protein
3) Message is propagated downstream through signal transducer proteins that bind to the activated messenger-receptor complex
Describe how the Insulin Receptor functions
1) Insulin binding activates tyrosine kinase activity
2) Autophosphorylation of β-subunits, activating the receptor
3) Insulin receptor substrate (IRS) binds receptor and is phosphorylated on tyrosine residues
4) SH2-domain proteins bind phosphotyrosine residues on IRS at multiple sites
5) The different sites that bind: ADAPTER PROTEIN GRB2 -> activation of Gas and the MAP kinase pathway, PI 3-KINASE -> activation of protein kinase B (PKB), PLCγ binds and is activated
What does the insulin receptor exist in the membrane as?
A preformed dimer (α and a β subunit)
Describe how JAK-STAT Proteins function
1) Receptors bind cytokines, dimerise and bind JAKs
2) JAKs phosphorylate each other and the receptor
3) Receptor binds and phosphorylates STATs
4) STATs dissociate from receptor, dimerise, translocate to nucleus
What are Signal Transducer Proteins (STATs)?
Gene-specific transcription factors
