L7 Cell Communication Flashcards
Signal types
contact dependent, synaptic, paracrine, endocrine
dpp
ligand
Example of contact dependent signalling
membrane bound signalling molecule
Paracrine signalling
secreted factor that interacts with extracellular matrix components
Endocrine signalling
produced by adrenal glands (mostly), wide range of physiological responses
Cell responses to signalling
altered metabolism, altered gene expression, altered cell shape or movement
Examples of effector proteins in cell signalling
metabolic enzyme, gene regulatory protein, cytoskeletal protein
Example of altered gene expression
expression of iroquois family genes in E12 mouse embryo
Example of altered cell shape or movement
human neutrophil chasing signal given off by saphylococcus aureus
Example of how cells respond to signal
french flag model
bicoid gradient function
defines anterior parts of resulting embryo
What do thresholds of signal trigger
on/off gene expression
What is the fastest cell response to signalling
changing structure of existing protein
What is the slowest cell response to signalling
changing protein levels via gene expression
Disease caused by signalling mis-regulation
myeloproliferative neoplasms, chronic myeloid leukaemia
Myeloproliferative neoplasm mutation
JAK2 V617F mutation in negative regulatory domain
Chronic myeloid leukaemia mutation
BCR-Abl fusion protein
BCR-Abl fusion protein effect
sustained Abl tyrosine kinase expression by the Bcr promoter/enhancer region
Signalling regulation points
ligand, receptor, transduction of signal, effectors can feedback
JAK/STAT pathway regulation
down regulation by SOCS negative regulator
Notch pathway regulation
lateral inhibition
Post-translational signalling regulation
phosphorylation, GTP binding
GEF function
GDP to GTP exchange factor
Ras function
growth control
Rho function
cytoskeleton
rab function
endosomal trafficking
Effect of modulating GAP and GEF levels
rapidly change the activity of the small GTPase
GAP
GTPase activating protein catalyst
Two major groups of protein kinase in eucaryotes
serine/threonine kinase, tyrosine kinases
Does protein kinase turn genes ON or OFF
ON
Type 1 kinase inhibitors
bind to active conformation of kinase
type 2 kinase inhibitors
bind and stabilise the inactive conformation of kinase
type 3 kinase inhibitors
occupy allosteric pocket that is adjacent to ATP binding pocket
type 4 kinase inhibitors
bind to allosteric pocket remote from ATP binding pocket
Key regulator of signalling
phosphatases
