Lecture 15: Signal Transduction/Lecture 16: Carbohydrates Flashcards
Classifications of cell signalling (3)
- Nature and origin of extracellular signal
- Type of receptor involved
- Physiological system
Ligands
Extracellular messenger molecules, bind to specific receptors, mainly bind membrane receptor proteins
Agonist
Ligand that initiates a biological response
Antagonist
Binds to receptor and causes no response, prevents other signalling molecules to bind and cause response
Kd
Dissociation constant, concentration of the ligand when the receptor is half-saturated, low values for Kd indicate high affinity
Kd= [R][L]/[R x L]
Second messengers
Propagate signals in cell, transient, kept at low intracellular levels until needed then are generated from abundant cellular precursors
Second messenger: cAMP
Derived from ATP by activation of adenylate cyclase
Removed by phosphodiesterase
Second messenger: phospholipids
Hydrolysis gives variety of second messengers
Ie. DAG, IP3
Second messenger: Ca
Cytosolic free Ca rises 100x from extracellular. and organelles sourced with ion activation
Skeletal contraction
Protein phosphorylation
Protein kinases transer PO4 from ATP to substrate proteins at Ser, Thr, and Tyr
Conserved catalytic and regulatory domains
Reversed by protein phosphatases
May modify activity or provide docking sites for signalling proteins
Target is usually protein kinases to amplify signal
Slower than Ca signalling
G-proteins
When bound to GTP, bind and activate downstream proteins
Intrinsic GTPase activity causes them to act as timers
1. Heterotrimeric G-proteins
2. Monomeric G-protiens
Heterotrimeric G-proteins
Directly activated by GPCRs
Monomeric G-proteins
Involved in signal transduction, small GTPases, Ras family
GPCR
7 transmembrane domains as alpha helices
Ligand binding to the outside causes conformational change that activates G-protein on the inside
GPCR activation of Protein Kinase A
- Hormone binds to GCPR
- Activation of Gs protein, alpha subunit dissociates and activated adenylyl cyclase
- Adenylyl cyclase makes cAMP, which acts on the regulatory subunits on PKA
- PKA activated when regulatory subunits interact with cAMP and dissociate from catalytic subunits
Receptor Tyrosine Kinase
Single transmembrane domain, respond to ligand binding by dimerizing, activates internal kinase domain and auto/cross-phosphorylate Tyr resides
Tyr (phosphorylated) act as docking sites for other proteins, uses modular protein domains to recruit signalling molecules and cause downstream responses
Ras
Monomeric G protein, involved in many RTK signalling pathways leading to cell proliferation
Interacts with multiple downstream signalling proteins when bound to GTP
Mutations near active site impair its GTPase activity leaving it always on
GlyH12
Active site of Ras
Mutations near site leave protein constitutively active
Ras mutations are present in 30% of humans cancers
Oncogenes
Cancer causing genes
Accelerates cell growth, reduced apoptosis, mitosis before DNA damage corrected, reduced/abnormal DNA repair, abnormal gene expression
(Also caused by loss of function of tumour suppressor genes)
Carbohydrates
Hydrates of carbon, general formula (CH2O)n, where n is greater than/equal to 3
Major roles: energy from diet, structural support, molecular recognition
Monosaccharide or polymers
Linear or branched
Glycosidic bonds
Attached carbohydrate monomers to form oligo/polysaccharides
Between hydroxyl groups to cause loss of H2O
Monosaccharides
Classified by:
- Nature of carbonyl group: aldoses, ketoses
- Number of carbons (numbered from carbonyl end)
- Ring size
- Stereochemistry
Aldoses
Monosaccharide that contained an aldehyde
Ketoses
Monosaccharide that contains a ketone
