Cell Signalling Flashcards
1
Q
Cell Signalling Pathway
A
- extracellular signal molecule
- receptor protein activation (conformational change in receptor)
- intracellular signalling proteins for signal transduction downstream
- effector proteins
- altered gene expression/metabolism/cell shape
2
Q
Types of Intercellular signalling
A
- contact dependent (contact via membrane bound signal/receptor)
- synaptic
- growth factors, hormones, cytokines
2. paracrine (small distance local mediators)
4. endocrine
3
Q
Cytokines
A
secreted by immune cells and modulate immune response
4
Q
Chemokines
A
subset of cytokines functioning as chemoattractants
5
Q
Hormones
A
produced by endocrine glands and distributed by bloodstream
6
Q
Growth factors
A
stimulate cell growth/differentiation
7
Q
Hydrophobic signal molecules
A
- cross plasma membrane directly
- mainly steroids or sex hormones
- once activated by hormone binding, nuclear receptors translocate to the nucleus and bind to DNA to regulate gene expression
8
Q
Signal Integration
A
- process of responding correctly to a number of different signals
- ie. multiple different signals integrate to provoke a process
9
Q
Signalling Context
A
- same signal molecule elicits different response
- context dependent
- acetylcholine can bind to heart pacemaker cells to decrease firing, salivary gland cells to secrete enzymes, and skeletal muscle cells to stimulate contraction
10
Q
Receptor State Changes
A
- conformational changes in proteins link signal inputs to outputs
- can cause PTMs, complex formation/dissociation, changes in localisation within cells
- inputs can change the protein at each signalling ‘node’ from off to on
11
Q
Effects of PTMs
A
- promote/prevent protein binding
- change conformation or activity
- change subcellular localization
- change proteolytic stability
12
Q
Post Translational Modifications
A
- writer: addition of modification
- reader: protein binding to PTM to carry on signal
- eraser: eraser of modification
- eg. phosphorylation of tyr, ser, threonine
- readers bind to phos. residue to mediate signalling and lead to output
13
Q
Example of PTM
A
- tyrosine kinase/phosphatase with SH2 domain
- receptor signalling - histone acetyl transferase/deacetylase with bromo domain
- increased transcription - ubiquitin ligase/deubiquitinase with UIM domain
- DNA damage response
14
Q
Protein kinase
A
- human kinome is 500 kinases (400 ser/threonine)
- conserved structure:
- N lobe and C lobe
- ATP substrate binding pocket in cleft
- gamma P of ATP transferred to protein
15
Q
Regulation of Kinases
A
- regulation by conformational changes and phosphorylation of activation loop
Inactive: - C helix in up conformation
- Lys-Gly salt bridge not formed
- activation loop blocks ATP binding site for autoinhibition
Active: - C helix in down conformation
- salt bridge formed
- activation loop moves out of ATP binding site and is phos.