Topic 11: Cell Signalling Flashcards
1
Q
4 Steps to Cell Signalling
A
- signalling molecules are released (ligands)
- recognition of the signalling molecule by target cell (receptors)
- signal transduction
- Final impact on target cell and subsequent impact on organism as a whole
2
Q
Signal Transduction
A
- the conversion of the extracellular signal into intracellular instructions
3
Q
Modes of communication
A
- direct interaction of a cell with its neighbour
- action of diffusible signalling molecules overs a distance
- some carry signals long distances, others act locally
- cell communication and signal transduction increases in complexity with multicellular organisms
- cell to cell
- paracrine
- autocrine
- endocrine
4
Q
5 Classes of Ligands (signalling molecules)
A
- Steroid hormones
- Eicosanoids
- Neurotransmitters
- Peptide hormones and polypeptide growth factors
- Simple gases
5
Q
Steroid Hormones
A
- small hydrophobic molecule (derived from lipid cholesterol)
- diffuses across cell membrane
- endocrine, paracrine, autocrine modes of action
- bind to intracellular receptors (Nuclear Receptor Superfamily)
6
Q
Eicosanoids
A
- Prostaglandins
- hydrophobic (synthesized from lipids) and are rapidly broken down
- paracrine or autocrine modes of action
7
Q
Neurotransmitters
A
- acetylcholine, dopamine
- hydrophilic molecules that don’t cross the cell membrane
- endocrine, paracrine, autocrine
- bind to cell surface receptors
8
Q
Peptide Hormones and Polypeptide Growth Factors
A
- insulin, epidermal growth fact
- largest and most variable class
- primarily hydrophilic and can’t cross the cell membrane
- endocrine, paracrine, autocrine modes of action
- bind to Cell Surface Receptors
9
Q
Simple Gases
A
- nitric oxide and carbon monoxide
- can move across the cell membrane (passive)
- paracrine mode of action
- bind directly to enzymes, do not use receptors
10
Q
2 Classes of Receptors
A
- Intracellular Receptors
- Nuclear Receptor Superfamily - Cell Surface Receptors
- G-protein coupled receptors
- receptor protein tyrosine kinases
- cytokine receptor superfamily
11
Q
Nuclear Receptor Superfamily
A
- molecules bind these receptors include steroid hormones and thyroid hormones (small, hydrophobic)
- receptors are intracellular proteins (not associated with the membrane)
- these receptors + ligand = transcription factors
- receptors contain both a ligand binding domain and a DNA binding domain
12
Q
Glucocorticoid Action
A
- inactive when bound to a chaperone
- become active when bound to a ligance
- 2 active receptors form a dimer
- dimer translocates to the nucleus
- dimer associates with the co-activator protein HAT
- hormone complex binds to a specific DNA binding site and activates gene transcription
- GLUCOCORTICOID RECEPTOR + LIGAND + HAT COACTIVATOR = ACTIVE GENE TRANSCRIPTION
- nuclear receptors transduce signal from ligand to DNA
- final effect: increase in transcription of a specific gene
13
Q
Gene Regulation by Thyroid Hormone Receptor
A
- thyroid hormone receptor (dimer) is bound to DNA either with or without ligand
- without ligand: receptor binds to corepressor HDAC to repress gene transcription
- hormone present: binds receptor, changing conformation to disassociate from HDAC and associate with HAT allowing gene transcription
14
Q
HDAC
A
- co-repressor
15
Q
HAT
A
- co-activator
16
Q
G-Protein Coupled Receptors
A
- largest family of cell surface receptors
- can bind a variety of ligands
- signals are transmitted to intracellular targets via an intermediary protein (Gprotein)
- contains 3 subunits: alpha, beta, gamma
- transmembrane proteins typically with multiple transmembrane domains
17
Q
Activation of G Protein
A
- extracellular receptor domain binds the ligand
- causes conformational change allowing cytosolic domain to activate a G protein
- alpha subunit dissociate from and carries signal to intracellular target (adenylyl cyclase)
18
Q
Tyrosine Kinase Receptors
A
- CSR linked to intracellular enzymes
- have one transmembrane domain
- enzyme activity by part of intracellular domain of receptor OR separate protein associated with intracellular domain
- receptors dimerize when bound to ligand
19
Q
Tyrosine Kinase Receptors Activation
A
- activate receptors by phosphorylating tyrosine residues on both the receptor and target substrates
- phosphorylated can then associate with downstream targets thereby initiating a signalling cascade
- proteins such as insulin and multiple growth factors recognize these receptors
20
Q
Dimerization and Autophosphorylation of Receptor Protein-Tyrosine Kinases
A
- ligand binds receptor causing dimerization followed by cross phosphorylation of both receptor dimers
- receptors can associate with downstream signalling molecules which begins a signalling cascade
21
Q
Activation of Nonreceptor Tyrosine Kinase
A
- nonreceptor tyrosine kinases are associated with receptors that contain no catalytic activity (cytokine receptors)
- ligand binding induces dimerization and active tyrosine kinases to autophosphorylate themselves and receptor
