What are the two types of cell-cell signalling?
- direct interaction of a cell with other cells
2. action of diffusible signalling molecules over a distance
What are the modes of signalling by secreted molecules?
Endocrine, paracrine, and autocrine
What is the function of signalling molecules?
Transmit information between cells of multicellular organisms.
How do signalling molecules transmit their information?
By binding to receptors on/in target cells.
What are the 5 classes of ligands (signalling molecules) in animal cells?
- steroid hormones (estrogen, glucocorticoids)
- eicosanoids (prostaglandins)
- neurotransmitters (acetylcholine, dopamine)
- peptide hormones and polypeptide growth factors
- simple gases
What is the structure of steroid hormones? What are its modes of action? Where does it bind?
- small hydrophobic molecule, diffusible across cell membranes
- endocrine, paracrine, and autocrine modes of action
- bind to intracellular receptors (nuclear receptor superfamily)
What is the structure of eicosanoids? What are its modes of action? Where does it bind?
- hydrophobic molecule synthesized from lipids in the plasma and nuclear membranes, are synthesized when needed and broken down rapidly
- paracrine or autocrine modes of action
- bind to cell surface receptors
What is the structure of neurotransmitters? What are its modes of action? Where does it bind?
- hydrophilic molecules that do not cross the cell membrane
- endocrine, paracrine, and autocrine modes of action
- bind to cell surface receptors
What is the structure of peptide hormones and polypeptide growth factors? What are its modes of action? Where does it bind?
- largest and most variable class, primarily hydrophilic and cannot cross the cell membrane
- endocrine, paracrine, and autocrine modes of action
- bind to cell surface receptors
How do simple gasses move across the cell membrane? What are their modes of action? Where do they bind?
- move across the cell membrane via passive diffusion
- autocrine and paracrine modes of action
- bind directly to second messenger or enzymes (do not use receptors)
What are receptors?
Proteins that undergo a conformational change when they interact with their ligand
What does a change in conformation of receptors allow for? What does this initiate? What does it often involve?
- Allows the receptor to interact with other intracellular molecules
- initiates a cascade of reactions resulting in cell changes
- often involves modulation of transcription factors and changes in gene expression. May also involve modulation of enzymes or ion channels
What ligands are associated with the nuclear receptor superfamily? What are their characteristics?
- ligands include glucocorticoids, steroid hormones, and thyroid hormones
- receptors are intracellular proteins (not associated with the membrane)
- these receptors are transcription factors, containing both a ligand binding domain and a DNA binding domain
What is involved in glucocorticoid action? (6 steps)
- glucocorticoid is inactive when bound to the Hsp90 chaperone
- becomes active when bound to the ligand
- two active receptors form a dimer
- the dimer translocates to the nucleus
- the dimer associates with the co-activator protein HAT
- the resulting hormone complex binds to a specific DNA binding site and activates gene transcription
How does gene regulation by the thyroid hormone receptor occur? (3 steps)
- thyroid hormone receptor (dimer) is bound to DNA with or without the ligand
- without the ligand, receptor binds the corepressor HDAC to repress gene transcription
- when hormone is present, it binds the receptor and changes its conformation to dissociate from HDAC and associates with the coactivator HAT, allowing transcription
What are the characteristics of G protein coupled receptors?
- largest family of cell surface receptors
- can bind to a variety of ligands including hormones, neurotransmitters, and peptides
- they are transmembrane proteins with multiple transmembrane domains
What are the three subunits of heterotrimeric G proteins?
alpha, beta, and gamma
What is the process of G protein regulation? (3 steps)
- G protein is in inactive state. Hormone binding stimulates the release of GDP in exchange for GTP
- G protein is in active state. The activated GTP-bound alpha subunit and beta-gamma complex dissociate from the receptor and interact with their targets
- activity of the alpha subunit terminated by hydrolysis of the bound GTP. Inactive GDP-bound alpha subunit reassociates with the beta-gamma complex
What are the characteristics of tyrosine kinase receptors?
they are cell surface receptors linked to intracellular enzymes and typically have one transmembrane domain
Where can kinase enzyme activity reside?
either in the intracellular domain of the receptor itself or in a separate protein associated with the intracellular domain
When do TK receptors dimerize? What does this activate?
- dimerize when bound to the ligand
- activates the receptors via phosphorylation of tyrosine residues on both the receptor itself and the target substrates
What do phosphorylated tyrosine kinase receptors interact with?
Interact with proteins that contain an SH2 domain (downstream signalling molecules)
What are nonreceptor tyrosine kinases associated with?
Associated with receptors that contain no catalytic activity
What is intracellular signal transduction?
A chain of reactions that transmit chemical signals from the cell surface to their intracellular targets
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Structure and Diversity of Cells27
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Molecular Composition of Cells40
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Nucleus and Genomes9
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DNA Replication0
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Transcription and RNA Processing0
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Protein Synthesis and Processing0
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Protein Sorting0
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Mitochondria, Cholorplasts, and Peroxisomes57
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Cell Signalling39
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Membranes and Cell Surface34
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Cytoskeleton and Cell Movement47
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Extracellular Matrix and Cell-Cell Interactions32
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The Cell Cycle & Apoptosis64
