Signalling Jargon Flashcards
Activated or constitutively activated mutants
An expressed
activated form of a signalling molecule (e.g., an oncogene) can gen signals in
the absence of a ligand
Adaptor proteins
Proteins lacking enzyme activity that mediate physical
interactions between proteins.
AhR
Arylhydrocarbon receptor
AKT
aka PKB (protein kinase B)
amplification
The use of enzymes (often acting sequentially in a cascade) to turn a single ligand receptor interaction into lots of intracellular activity. Ligand-receptor interaction at the cell surface converted into lots of activity (e.g., 2nd messengers) inside the cell. Depends on the catalytic ability of an enzyme to produce, or activate, >1 product molecule
AP1
a TF complex composed of Fos and Jun
AR
androgen receptor
Arnt
Arylhydrocarbon receptor nuclear translocator
autocrine signalling
when a cell both makes the ligand or signal and
also possesses a receptor which allows it to respond to the ligand.
C2 domain
binds to phospholipids (and some proteins) in either calcium dependent or independent manner
CaM
Calmodulin. A calcium binding protein that mediates many aspects of
calcium signalling in cells
CaMK
Calmodulin dependent kinase. A kinase regulated by calmodulin
DAG
1,2-diacylglycerol, a membrane bound second messenger formed which
phospholipids are broken down by phospholipase C enzymes. Involved in the
activation of some isoforms of PKC.
dominant negative mutants
Mutants of signalling proteins which can interact with upstream and downstream components of a signalling cascade but
cannot transmit a signal
DRE
dioxin response element
effector proteins
Enzymes that transduce ligand-activated signals into
the cell. May catalyse the formation of second messenger molecules
EGF
Epidermal growth factor. A peptide ligand that actives the EGF receptor PTK
endpoint (or readout)
any cell activity studied to determine whether it
is involved downstream of a signalling molecule
epitope tag
a short protein seq introduced into a protein of interest using molecular biology techniques and to which you have a well characterised Ab. Allows detection of an expressed protein.
ER
oestrogen receptor
ERE
oestrogen response element
FGF
Fibroblast derived growth factor. A family of peptide growth factors that
activate members of the FGF receptor PTK family
Fos
a TF (and oncogene) which binds to Jun to form the AP1
complex
Fura 2
a calcium sensitive fluorescent dye
fusion proteins
Like epitope tags except the fused protein has an activity
of its own. In the case of GST fusion protein it can bind glutathione. This allows the
fusion protein to be captured without a specific Ab. In the case of GFP it allows the location of the fusion protein in live cells to be examined by looking for
fluorescence
Fyn
a Src family, cytosolic PTK
GAP
GTPase activating protein. -ve regulator of small G proteins e.g. Ras. Binds to the activated form of the small G protein and stims the intrinsic activity of the small G protein to hydrolyse GTP to GDP thus converting the G protein back to its inactive state
GEF
Guanine nucleotide exchange factor – a family of protein that facilitate the
removal of GDP from small G proteins during their activation
GFP
green fluorescent protein
GPCR
G protein coupled receptor. A type of receptor characterised by 7
mem spanning domains that couples to G proteins to propagate a signal within the cell.
G proteins
Proteins that bind to guanine nucleotides (GTP and GDP).
These are active when bound to GTP. Inactive when bound to GDP
GR
glucocorticoid receptor
Grb2
an adaptor protein composed solely of SH2 and SH3 domains that couples
PTK signalling to Ras activation
GRE
glucocorticoid response element
GST
glutathione S-transferase
heterotrimeric G protein
G protein activated by GPCR and composed of G alpha, G beta and G gamma subunits
HRE
hormone response element
ILK
integrin-linked kinase
immunoprecipitation
A technique used to capture or concentrate specific proteins or complexes. Abs can be coupled to polymer beads and used to affinity capture their respective Ag.
Captured protein can be used for: I) Enzyme assay. II) To investigate associated
proteins.
inhibitors
An small molecule, cell permeable inhibitor against a known signalling component can be used to ask whether this component is involved in the pathway under study
InsP3
aka IP3 and Ins(1,4,5)P3 Inositol trisphosphate. A second messenger
formed by the action of PLC on inositol phospholipids. InsP3 binds to receptors on
intracellular mems and leads to the release of calcium from intracellular stores
ionotropic receptor
receptors that lead to changes in ion flux across mems
ITAM
immune tyrosine activation motif
ITIM
immune tyrosine inhibitor motif
JAK
a cytosolic PTK
Jun
a TF that together w/ Fos makes up the AP1 TF
Kinases
Enzymes that transfer phosphate groups (PO4) from ATP to their
substrates
e.g., serine kinases phosphorylate the hydroxyl group serine residues on proteins
protein tyrosine kinase phosphorylate the hydroxyl group tyrosine residues on
proteins
phosphatidylinositol 3-kinase phosphorylates the 3’ hydroxyl group of inositol
phospholipids
Lck
a Src family, cytoslic PTK
ligands
External signal, agonist, stimuli or first messenger. Binds to a larger
(receptor) molecule.
e.g., Proteins, peptides, hormones, lipids, small molecules, etc.
LY294002
A widely used PI3K inhibitor
MAPK
aka ERK and MAP kinase - a cytosolic serine /threonine kinase
MEK
aka MAPKK (MAP kinase kinase) a cytosolic serine/threonine kinase
downstream of Raf that phosphorylates and activates MAPK.
metabotropic receptor
Receptors that leads to activation of enzymes,
often those assoc with metabolism
molecular recognition
Interactions between signalling molecules
which provide specificity to the pathway, e.g., between ligand and receptor, between adaptor proteins and effector proteins, between signalling domains and other signalling proteins or mem lipids
molecular switch
A biological switch can exist in either an active or
inactive conformation and can be switched between the two states, e.g.,
phosphorylation and G-protein switches
Myc
a TF & known oncogene
NO (nitic oxide)
a novel second messenger
Non-enzymatic signalling domains or modules
Small independently folding modules (~100 amino acids in size), identified by seq
homology, found in a wide range of proteins with no obvious common function.
Function to regulate signalling molecules activity and cellular localisation via
protein-protein and protein lipid interactions.
NOS (nitric oxide synthase)
The enzyme that generates Nitric Oxide
the second messenger gas. Comes in i, e and n flavours (inducible, endothelial and
neuronal)
PDGF
Platelet-derived growth factor. A dimeric peptide growth factor that
activates the platelet-derived growth factor receptor (a PTK receptor)
PDZ domain
binds to S/T x V motifs at C-terminus of proteins
PH domain
binds to inositol phosphates and inositol phospholipids (poss to some proteins too)
phosphatases
Remove phosphate groups from their substrates.
Antagonise the action of kinases
phosphorylation
addition of a phosphate (PO4) group to a molecule
catalysed by a specific kinase enzyme protein
Phosphatidylinositol (PtdIns) and phosphoinositides
(PIs)
A family of mem lipids w/ an inositol ring exposed to the cytoplasm that can be phosphorylated by PtdIns kinases. The phosphorylated lipids form mem docking sites for domains in signalling proteins such as the PH domain.
phosphospecific Abs
Abs which recognise a molecule only when it has been modified by the addition of a phosphate group at a specific
site
PKA
protein kinase A. A cytosolic protein serine/threonine kinase activated by
cAMP
PKB
Protein kinase B a cytosolic serine threonine kinase (aka Akt) which is activated by PI 3-kinase signalling
PKC
a family of cytosolic protein serine/threonine kinases activated by calcium,
diacylglycerol (DAG) and phospholipids
PLC
Phospholipase C, an effector which catalysed the cleavage of mem phospholipids incl phophatidylinositol, 4,5P2 to diacylglycerol and inositol
trisphosphate (Ins(1,4,5)P3). Some isoforms are regulated by GPCR signalling and
some by PTK signalling
PP1, PP2A, etc
a family of protein serine/threonine phosphatases
PPAR
peroxisome proliferator activated receptor
protein domain or module
a region of a protein, often defined by seq homology, which can function independently.
PR
progesterone receptor
PTEN
a lipid phosphatase and tumour suppressor gene, that negatively
regulates PI 3-kinase signaling by removing 3’ phosphates from the inositol ring
PTK
protein tyrosine kinase
PTP
protein tyrosine phosphatase
Raf
a cytosolic protein serine/threonine kinase activated by Ras. Aka MAP
kinase kinase kinase or MAPKKK. A known oncogene
RAR
retinoic acid receptor
Ras
a prototype small monomeric G protein (and known oncogene) activated
downstream of many PTKs. Ras couples to PI3K and MAPK signalling
receptors
proteins, mainly inserted into plasma mem, to which ligands specifically bind.
reception phase
Reception involves the target cell’s detection of a signal
coming from outside the cell. A chemical signal is “detected” when it binds to a
cellular protein usually at the cell surface
response phase
In this third phase of cell signalling, the transduced signal finally triggers a specific cellular response. This response can be a change in almost
any imaginable cellular activity
RSK
a cytosolic serine threonine kinase activated by MAP kinase
SDS-PAGE
SDS-polyacrylamide gel electrophoresis. A method for separating proteins in a gel in an electric current on the basis of their molecular
weight. SDS is a negatively charged detergent that binds to proteins and denatures them. The amount of SDS bound is proportional to the number of amino acids in
the protein and thus the final net negative charge of the SDS bound protein will be related to the proteins size
second messengers
Small chemical messengers that carry signalling
information by diffusion from one part of a cell to another.
– e.g., cyclic nucleotides (cAMP), Ins(1,4,5)P3, calcium, nitric oxide (NO)
SH2 domain
binds to tyrosine phosphorylated protein sequences.
SH3 domain
binds to proline-rich target sequences, which form a helical structure
Shc
adaptor protein involved in PTK signalling
SHIP
an inositol lipid phosphatase that removes the 5’ position phosphate from
the inositol ring.
Shp
a protein tyrosine phosphatase
signal transduction
mechanisms by which a cell is able to respond to changes in its env
signal transduction pathway
Cells receive/recognise external stimuli and convert (transduce) that recognition event into a response within the cell. The response is usually a change in one or more cellular activities. The series of steps that make up this process are called a signal transduction pathway
SOS
Son of Sevenless, a GEF protein involved in activation of Ras
Src
the prototype cytosolic PTK that defies the Src family
SRE
steroid response element
Syk
a cytosolic PTK
target proteins
proteins that mediate a signalling pathway endpoint - enzymes, motor proteins, TFs…
TCR
T cell receptor
complex of proteins that mediate T Cell signalling
TR
thyroid hormone receptor
transduction phase
The transduction step(s) converts one type of signal
(e.g., the initial stimulus or ligand binding) into another signal (e.g., an internal or
2nd messenger) and may also amplify the signal in the process
western blotting
Proteins from the SDS-PAGE gel are transferred to a
nitrocellulose membranes generating a replica of the gel. This can then be probed
with a labelled antibody to determine the presence, absence or level of a particular protein or protein modification (eg., phosphorylation)
wortmannin
a widely used PI3K inhibitor
