BIOL130 Lecture Notes - Protein Kinase, Signal Transduction, Adenylyl Cyclase
26 Feb 2013
School
Department
Course
Professor
Cell Communication
general concepts
o endocrine / paracrine / neural
o receptor protein, target cell, signal transduction
o fast vs slow responses
o intracellular vs cell-surface receptors
intracellular receptors
o mechanism of action, nuclear receptor family of transcription factors
cell-surface receptors
o second messengers
o molecular switches
phosphorylation, kinases / phosphatases, phosphorylation cascades
GTP-binding proteins (G-proteins)
o 3 classes of cell-surface receptors:
1) ion channel-linked
2) G-protein coupled receptors (GPCRs), a, b, g subunits
3) enzyme-linked receptors
o a closer look at GPCRs and enzyme-linked receptors:
GPCRs - downstream targets of activated G-proteins
1) ion channels e.g. Ach-R in cardiac muscle, K channels
2) activate enzymes associated with cytosolic face of membrane
2a) adenylyl cyclase cAMP PKA
2b) phospholipase C IP3 + DAG Ca2+ PKC
Ca2+ as an intracellular signal; calmodulin, CaM-kinases
enzyme-linked receptors
receptor tyrosine kinases (RTKs) and Ra
o RTK, Ras and cancer
Why Cells Communicate
single celled organisms
o ‘social life’ – yeast mating
multicellular organisms, coordination of
o development (from single cell to trillions of cells)
o growth
o coordinating ‘whole body’ growth and development with environment
o day to day physiology
Long vs. Short Range Communication
Endocrine
o if you have the receptor, you can hear the signal (hormone carried in blood stream)
Paracrine
o if you have the receptor and are in close distance, you can hear the signal (local mediator)
Neuronal
o Long distances (down axon to neurotransmitter, across synapse)
Contact-Dependant
o Cells touch (membrane bound signal molecule)
Signalling Pathways
Pathway
o signalling molecule synthesized and released by signalling cell
o signal molecule travels to target cell
o signal binds to receptor protein on / in target cell
o signal transduction
o change in target cell behaviour
cell shape, movement
metabolism, secretion
gene expression
Same signal can cause different responses, depending on the target cell.
o acetyl choline (signal)
Heart muscle cell
decreased rate and force of contraction
Salivary gland cell
Secretion
Skeletal muscle cell
contraction
Fast/Slow Responses
o Slow (minutes to hours)
When signal binds to receptor, it can affect nucleus, which will result in RNA being transcribed
which will alter protein synthesis, causing altered cytoplasmic machinery and eventually altered
cell behaviour
o Fast (seconds to minutes)
When signal binds to cell-surface receptor protein, it can follow the intracellular signalling
pathway, cause altered protein function, altered cytoplasmic machinery and eventually altered
cell behaviour
Receptors
Cell Surface Receptor (on plasma membrane)
o Signal molecule is hydrophilic
Bind to receptor protein on plasma membrane
Relay, transduction and amplification of message through secondary messengers
small (non-protein) molecules that relay signals from cell surface receptors to target
molecules within cell (through cytoplasm)
integration
distribution of message to effector proteins (metabolic enzyme, cytoskeletal enzyme,
transcription regulator)
causes cell response
o Molecular Switches (intracellular signal molecules)
turning off a signal is just as important as turning it on
Turn on: protein kinase (transfer phosphate group from ATP to phosphate)
Turning off: protein phosphatase (remove phosphate group)
each activation step in a cascade needs to be inactivated
Signalling by Protein Phosphorylation
activity of a protein regulated by phosphorylation depends on balance between
activities of its kinases and phosphatases
Document Summary
Gtp-binding proteins (g-proteins: 3 classes of cell-surface receptors, ion channel-linked, g-protein coupled receptors (gpcrs), a, b, g subunits, enzyme-linked receptors, a closer look at gpcrs and enzyme-linked receptors: Gpcrs - downstream targets of activated g-proteins: ion channels e. g. ach-r in cardiac muscle, k channels, activate enzymes associated with cytosolic face of membrane. 2b) phospholipase c ip3 + dag ca2+ pkc. Enzyme-linked receptors receptor tyrosine kinases (rtks) and ra: rtk, ras and cancer. Multicellular organisms, coordination of: development (from single cell to trillions of cells, growth, coordinating whole body" growth and development with environment, day to day physiology. Endocrine if you have the receptor, you can hear the signal (hormone carried in blood stream) Paracrine if you have the receptor and are in close distance, you can hear the signal (local mediator) Neuronal: long distances (down axon to neurotransmitter, across synapse) Contact-dependant: cells touch (membrane bound signal molecule)