Intracellular Signalling Flashcards
Definition of endocrine
Signal produced by cells in 1 body part, travels in blood to target cells elsewhere
Definition of autocrine
Signal acts on same cell that produces it
Definition of paracrine
Signal produced by cell, acts on cells close by
Definition of contact dependent
Signal is integral part of 1 cell, interacts directly with another cell
Definition of neuronal
Electrical signal transmitted down cell, message passed to another via synapse
Definition of G proteins
Guanine nucleotide binding proteins act as molecular switches inside cells. Involved in transmitting signals
Function of cellular responses
Change metabolic activités
Secrete and release
Changes in gene expression
Sensory perception
Factors that act as extracellular signals
Amino acids + derivatives Steroids Prostaglandins (eicosanoids) Proteins and peptides Gases
How cells signal to each other
Endocrine Autocrine Paracrine Contact dependent Neuronal
Characteristics of receptors/signals
Receptor must be expressed in order to respond to signal
High selectivity and affinity
Signal can bind to different receptor types
Signal eventually turned off
Location of receptors
Cell surface
Intracellular receptors
What happens with a receptor on the cell surface
Hydrophilic hormone
Binding triggers internal response without hormone entering
What happens with an intracellular receptor
Hydrophobic hormone
Binds to internal receptor, triggers internal response
Crosses plasma membrane
Types of signalling
Binding of signal to receptor by
Depolarization of signal to receptor due to ion flow
Direct transcription factor activation
Generation of 2ndary message in cell
Direct activation of enzymatic kinase cascade
What happens in depolarization of membrane due to ion flow?
Ach (signal) binds to nicotinic acetylcholine receptor
Ion channel opes to allow Na+, K+, Ca2+ in
What do steroid hormones have?
Hormone binding domains
DNA binding domain
Interacting with other transcription factors domain
What happens in direct activation of transcription factors
Binding of steroid induces conformational change, allows DNA binding, activation of target gene transcription
DNA binding domain is sequence specific
Transcription factors = ligand dependent
What is the secondary messenger model
Signal binds to transmembrane receptor (1st messenger)
Triggers other molecules in the cell, (acts as 2nd messenger)
Structure of guanine nucleotide binding proteins
Inactive state, aby
Dissociates into a by when GDP binds
Free active a subunit activates effector enzymes
Location of the G protein coupled receptor
Transmembrane a helix with 7 proteins
GPCR signalling to effector enzymes
Signal binds to receptor
G protein (GDP bound) associates w receptor
GTP/GDP exchange on G protein (GTP bound)
G proteins dissociate into a (GTP bound) and by subunits
a (GTP bound activates effector enzyme
Effector produces 2nd messenger
GTP hydrolyses to GDP, G proteins complex reassociates, end of signal
Structure of cAMP dependent protein kinase A (PKA)
Tetrameric enzyme, 2 regulatory, 2 catalytic subunits (r2c2)
When cAMP binds to both r, activates c subunits
How does CREB affect gene transcription?
PKA phosphorylates cAMP response element binding protein (CREB)
CREB binds to specific sequences in target genes, transcription stimulated
Gene expression can change if change is long term (starvation)
GPCR and IP3/DAG signalling
Signal molecule activates GPCR
Activated G protein a subunit activates phospholipase C
Activated phospholipase C cleaves IP3 from DAG
IP3 activates Ca2+ channel
DAG + Ca2+ activates PKC
Direct activation of enzymatic kinase cascade
Binding of EGF => dimerisation of intracellular domains => autophosphorylation of tyrosines
Tyr <= SH2 <= GRB2 <= SOS
Ras is broken down from GDP => GTP and triggers MAPKKK cascade
Ras
Monomeric G protein
GTP-Ras triggers kinase cascade
Has no 2ndary messenger
GDP-Ras => GTP-Ras
What is the Ras-MAP-kinase pathway
Mitogen activated protein kinase kinase kinase (MAPKKK) activates MAPKK
Activates MAPK
Activates transcription factor
GPCR and cAMP pathway
Molecule binds to extracellular binding GCPR site
Dissociated GTPa unit activates adenylyl cyclase
AC converts ATP => cAMP
cAMP activates PKA
PKA can activate CREB which affects transcription
