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GFP (Green fluorescent protein) Label proteins with immunofluorescence
VSVG Viral gene used to study temperature-sensitive movement of
proteins through endomembrane system
RNAi (RNA interference) Process in which cells produce siRNA
siRNA (Small interference RNA) Bind to specific mRNAs and inhibit the translation of these
mRNAs into proteins
Mannosidase II Enzyme synthesized in the ER that moves to Golgi where it
takes residence. Stains the medial Golgi network.
Oxygenases Oxygen transferring enzymes that carry out detoxification;
found in the SER
Cytochrome P450 family Part of the oxygenase family. Lack substrate specificity.
Metabolize many prescribed medications
Sarcoplasmic reticulum The smooth ER of skeletal and cardiac muscle cells.
SRP (signal recognition particle) Recognizes the signal sequence of the polypeptide and binds
to it and to the ribosome at the same time. This stops
temporarily the synthesis. Serves as tag enabling the complex
to bind to the cytosolic surface of the RER membrane.
SRP receptors The SRP interact with this receptor in order to bind to the RER
translocon.
Translocon A protein-lined channel embedded in the RER through which
the polypeptide moves from ribosome to lumen co-
translationally.
G proteins (GTP binding proteins) Participate in many key regulatory processes
GTP- active
GDP- inactive
Oligosaccharyltransferase Enzyme that adds carbohydrates to the nascent polypeptide
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PDI (protein disulfide isomerase) Protein-processing enzyme. Catalyzes the formation of
disulfide bonds.
Glycosyltransferases Catalyzes the addition of sugars to an oligosaccharide chain
Dolichol phosphate Lipid carrier embedded in the ER. Associated with
glycosylation.
Site for N-linked oligosaccharides (asparagine residues)
CDG Congenital diseases of Glycosylation caused by a mutation that
affects this process.
Calnexin ER chaperone
Calreticulin ER chaperone
Mannosidase I Found in cis Golgi-Network
Mannosidase II Found in medial Golgi-Network
UGGT Is a conformation sensing enzyme, (recognizes misfolded
proteins), that adds a single glucose residue back to one of the
mannose residue at the exposed end of the recently trimmed
oligosaccharide (RER N-linked oligosaccharide modification).
ERAD (ER-associated degradation) Process that ensures that aberrant proteins are not
transported to other parts of the cell.
UPR (unfolded protein response) A comprehensive response that occurs in cells whose ER
cisternae contain an excessively high concentration ofunfolded or misfolded proteins. Sensors that detect this
situation trigger a pathway that leads to the synthesis of
proteins that can alleviate the stress in the ER. Also it is believe
that it can lead to cell programmed death.
ERGIC (endoplasmic reticulum Golgi intermediate
compartment)
Soon after vesicles bud from the ER membrane, they fuse with
one another to form larger vesicles and interconnected
tubules in the region between the ER and the Golgi.
VTCs vesicular-tubular carriers that form in the ERGIC region; move
from the ER to Golgi complex through microtubules
Syalyltransferase Enzyme that places sialic acid at the terminal position of the
oligosaccharides.Reduced osmium tetroxide (OsO4) Stains cis-golgi network
Nucleoside diphosphate Enzyme that splits dinucleotides, stains the trans-Golgi
network.
COPII ER to Golgi
COPI Golgi to ER
Clathrin Golgi to endosomes, lysosomes and vacuoles
Sar1 Small G-protein that initiates vesicle formation. Associated
with COPII
Sec23 & Sec 24 Polypeptides of COPII coat. Bind as dimmer to help with the
vesicle formation.
Sec24 Binds the cargo receptorSec13 & Sec31 Subunits of the COPII coat (outer); provide flexibility to the
vesicle
KDEL Lys-asp-glu-leu, retrieval signal. If deleted, escaped ER proteins
(soluble) do not go back to the ER, instead they stay in the
Golgi and continue through the secretory pathway.
KDEL receptor An integral membrane protein that shuttles between the cis
Golgi and the ER compartments. Recognizes KDEL sequence
when escaped ER protein arrives to cis Golgi cisterna
KKXX Common retrieval sequences for ER membrane proteins.
Composed of 2 lysine and 2 residues of any kind.
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MPR (mannose-6-phosphate receptor) Integral membrane protein that span the TGN membranes.
Recognizes the lysosomal enzymes carrying mannose-6-
phosphate sorting signal.
GGAs Adaptor proteins that escorts lysosomal enzymes from the
TGN.
Golgins One class of fibrous tethering proteins that act in and around
the Golgi complex.
Rabs Small G-proteins that confer much of the specificity between
vesicle and target. Recruits specific cytosolic tethering proteinsto specific membrane surfaces.
SNARES Key proteins that mediate the process of membrane fusion. t-
SNAREs are located in the membranes of target
compartments. v-SNAREs incorporate into the membranes of
transport vesicles during budding.
Acid hydrolases Hydrolytic enzymes with optimal activity at an acid pH (found
in lysosomes and vacuoles, for example).
RME (receptor mediated endocytosis) Uptake of specific extracellular macromolecules (ligands)
following their binding to receptors on the external surface of
the plasma membrane.
AP2 Adaptor protein operating in connection with Clathrin-mediated endocytosis
Dynamin Large G-protein that is required for the release of Clathrin-
coated vesicle from the membrane on which it forms.
Phosphoinositides When phosphate groups are added to different positions of
the sugar ring of the phosphatidylinositol (PI). Can aid in
recruiting specific proteins, it can also induced conformational
changes.
LDL Receptor that delivers cholesterol to the cell. High levels are
associated with risk of heart disease.
Receptor down-regulation Mechanism by which cells regulate their ability to respond to
extracellular messengers.
Ubiquitin Tag for a protein to be endocited and destroyed
ESCRT 1- Sort ubiquitinated receptors2- Cause the membrane to innvaginate as a bud3- Release of the newly formed intraluminal vesicle
MVB (multivesicular bodies) Late endosomes that possess internal vesicles
PTS (peroxisomal targeting signal) Signal in the proteins destined for a peroxisome.
TOM Protein-import complex of the OMM (outer mitochondrial
membrane)
TIM Proteinimport complex of the IMM (inner mitochondrial
membrane)
HSP70 Maintains protein denatured (primary amino acid sequence
structure)
HSP60 Chaperona que se encuentra en la matriz y ayuda al doblez
(folding).
TIM22 Trasloca proteinas integrales
TIM23 Mueve hacia matriz de la mitocondria
Toc Chloroplast translocation complex. To the outside
Tic Chloroplast translocation complex. To the inside
Nuclear envelope Two cellular membranes that function as a boundary between
the nucleus and cytoplasm
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Nuclear lamina Provides structural support to the nuclear envelope, serves as
a site of attachment for chromatin fibers
Laminins Phosphorylation induces disassembly of the nuclear lamina
prior mitosis
NPC (nuclear pore complex) Gateway between the cytoplasm and the nucleoplasm; its not
a static structure
Nucleoporins Proteins of the NPC
NLS (nuclear localization signal) Stretch of positively charged amino acids at the C-terminus of
nuclear proteins that enables them to pass through the NPCNES (nuclear export signal) Present in proteins that will be exported from the nucleus to
the cytoplasm
Importin Move macromolecules cytoplasmnucleus (IN)
Importin / Importin complex that moves cargo into the nucleus
Importin is shuttled out into the cytoplasm with Ran-GTP
Importin exits with an exportin
Ran GTP- active, GDP- inactive
Drives the release of the cargo into the nuclear compartment
Ran-GTP High concentration INSIDE (nucleoplasm)
1. disassembly of imported complexes2. assembly of exported complexesRan-GDP High concentration OUTSIDE (cytoplasm)
RCC1 Promotes conversion from Ran-GDP to Ran-GTP
RanGAP1 Conversion of Ran-GTP to Ran-GDP
Exportin Move macromolecules nucleuscytoplasm (OUT)
GPCR (G-protein coupled receptors) Constitute the single largest superfamily of proteins encoded
by animal genomes. The amino-terminus is on outside of the
cell, with 7 alpha helices that transverse the plasma
membrane are connected by loops of varying length and with
the carboxyl-terminus is present on the inside of the cell.
G Where the guanine nucleotide-binding sites.cAMP Second messenger
Gs Couple receptors to adenylyl cyclase
Gq Activates PLC-
Gi Inhibits adenylyl cyclase
G12/13 Associated with excessive cell proliferation
PLC- Hydrolyzes phosphatidylinositol bisphosphate producing
inositol triphosphate (IP3) and diacylglycerol (DAG).
Activate through GPCRs
PLC-, PLC- Activate through RTKs
PLC- Activated by Ca2+
All PLC isoforms produce IP3to increase Ca
2+
GRK (G-protein-coupled receptor kinase) Form a small family of serine-threonine protein kinase that
specifically recognize activated GPCR, and phosphorylates
them (desensitization)
-Arrestin Form a small family of proteins that bind to GPCR and
compete for binding with heterotrimeric G-proteins.
RGS (regulators of G-protein signaling) Interaction with it increases the rate of hydrolysis by the G
subunit, accelerating the termination of the response.
PH domain A protein domain that binds to the phosphorylated inositol
rings of membrane boundphosphoinositides
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SH2 domain (Src-homology 2) Phosphorylated tyrosine binding domain.
Mediate phosphorylation dependent protein-protein
interactions
SH3 domain (Src-homology 3) Phosphorylated tyrosine binding domain.
Protein-protein/protein-cell membrane interaction
PTB domain (phosphotyrosine-binding) Phosphorylated tyrosine binding domain.
Asn-Pro-X-Tyr motif
IP3 (inositol 1,4,5-trisphosphate) Sugar phosphate. Small and soluble molecule capable of rapid
diffusion. They bind to specific receptors located in the SER.The receptor also functions as a Ca2+channel.
DAG (diacylglycerol) Lipid molecule that recruits and activates effector proteins
that bear a DAG-binding C1domain
Has PH domain
RTK (receptor protein-tyrosine kinases) Integral membrane proteins that contain a single
transmembrane helix and an extracellular ligand binding
domain. They are activated directly by extracellular growth
and differentiation factors or by metabolic regulators.
Autophosphorylationon tyrosine residues allows binding of
specific domains.
Tyrosine residues When phosphorylated, serve as docking sites for otherproteins
GAP (GTPase activating protein) Stimulate hydrolysis of bound GTP, which inactivatesthe G
protein. Shorten the duration of G-protein mediated response.
GEF (Guanine nucleotide-exchange factors) Proteins that bind to inactive monomeric G protein and
stimulate dissociation of the bound GDP (activates).
GDI (Guanine nucleotide-dissociation inhibitor) Proteins that inhibit the release of a bound GDP from a
monomeric G protein (inactivates).
STAT Transcription factor that contains SH2 domain. Important for
the function of the immune system.
*If TFs are not dimerized they wont move into the nucleus.
Kinases, phosphatases, phospholipases, GTPase Activated by RTKs and have SH2 domain
Cbl Receptor-binding protein. Has SH2 domain that can bind to
pTyr and catalyzes the addition of ubiquitin to the receptor
Ras-MAP kinase cascade Turned on in response to a wide variety of extracellular signals
and plays a key role in regulating vital activities such as cell
proliferation and differentiation.
Plasma membranecytosolnucleus
EGFR First RTK studied; binds EGF growth factor
EGF Growth factor that activates Ras-MAPK cascade
PDGF Growth factor that activates Ras-MAPK cascade
Grb2 Adaptor protein with one SH2 domain and two SH3 domains;
forms protein signaling complex
Sos Binds to SH3 domains in Grb2; GEF for Ras (activates)
Gab Binds to SH3 domains in Grb2
Ras Small lipid anchored GTPase
GTP: active
GDP: inactive
Raf (MAPKKK) Important signaling serine-threonine protein kinase. It is
recruited to the inner surface of the plasma membrane where
it can be activated by combining phosphorylation (membrane
bound) and dephosphorylation (soluble).
MEK (MAPKK) Kinase that phosphorylates (activates) ERK1 and ERK2
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ERKs (MAPK) Once activated, it moves into the nucleus to
phosphorylates transcription factors, protein kinases,
cytoskeletal proteins, apoptotic regulators, receptors, etc.
AKAP Scaffolding proteins involved in cAMP-driven pathways
Adenylyl cyclase Effector; activated by G protein subunit
cAMP Secondary messenger that participates in many cellular
processes
cAMP phosphodiesterase Destroys cAMP to terminate a response to stimuli
Guanylyl cyclase Effector; activated by NOcGMP Secondary messenger that participates in many cellular
processes
Important in sensory perception and muscle/blood vessel
relaxation
cGMP phosphodiesterase Destroys cGMP to terminate a response to stimuli
PKA Activated by cAMP. Has two regulatory subunits and two
catalytic subunits. Phophorylates glycogen synthase,
phosphorylase kinase, or can go directly into the nucleus and
phosphorylate CREB
PDK1 Has PH domain to interact with PIP3and phosphorylates PKB
(AKT)PKB
a.k.a. AKT
Has PH domain that interacts with PIP3
Mediates the response to insulin and other extracellular
signals
Regulates glucose transport and glycogen synthesis
mTOR Phosphorylates PKB
PKC Effector; interacts with DAG
Has important roles in cellular growth and differentiation,
cellular metabolism, cell death, and immune responses.
PKG Activated by cGMP
Triggers muscle relaxation and dilatation of blood vessels
GLUT4 Glucose transporter, in the presence of insulin it istranslocated from cytoplasmic vesicles to the plasma
membrane
Glycogen synthase Synthesizes glycogen
Unphosphorylated: ACTIVE
Phosphorylated: INACTIVE
GSK3 (glycogen synthase kinase-3) Inactivated when phosphorylated by PKB
Phosphorylase kinase Activated by phosphorylation of PKA.
Glycogen kinase Activation occurs when phosphorylated in a specific serine
residue by phosphorylase kinase.
Promotes glycogen breakdown/release of glucose.
Glycogen Stored excess glucoseGlucagon Stimulates breakdown of glycogen
Insulin Stimulates uptake of glucose by cells and glycogen storage
Epinephrine Stimulates breakdown of glycogen
PP1 (protein phosphatase 1) Remove phosphates from all of the phosphorylated enzymes
(glycogen synthase, phosphorylase kinase, glycogen kinase)
Dephosphorylation of glycogen synthase activates it
IRS Docking protein that supplies RTKs with additional tyrosine
residues for phosphorylation to create SH2 binding sites
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(scaffold for protein-protein interaction)
Interacts with RTK through PTB domain with pTyr 960 and has
a PH domain
PI3K Has two SH2 domains and one catalytic domain to
phosphorylate phosphoinositides at the 3 position of the
inositol rng
PIP3 Product of PI(4,5)P2phosphorylation that provides binding
sites for PH domains (in PDK1 and PKB)
CREB (cAMP response element binding protein) Transcription factor located in the nucleus that isphosphorylated by PKA, after which it binds as a dimer to DNA
sites
CRE (cAMP response element) Site in DNA where transcription factors bind and increase the
rate of initiation of transcription
TGACGTCA
Ca2+ Secondary messenger that binds to various targets and
triggers a lot of responses (ex. Muscle contraction and
exocytosis of histamine)
NO Diffuses between adjacent cells (paracrine signaling)
Activates guanylyl cyclase. Triggers muscle relaxation and
dilatation of blood vessels.Viagara cGMP phosphodiesterase inhibitor
NOS (nitric oxide synthase) Synthesizes nitric oxide
Phosphatases Remove phosphate groups from proteins
Kinases Add phosphate groups to proteins
Glucagon Epinephrine Insulin
GPCR GPCR RTK
cells of the pancreas Tyrosine derived cells of the pancreas
In response to low blood
sugar
In response to low blood
sugar
In response to high blood
sugar
Stimulates glycogen
breakdown into glucose
Stimulates glycogen
breakdown into glucose
Stimulates glucose uptake
and storage (glycogen)
Inhibit glycogen synthase Inhibit glycogen synthase Glycogen synthase is active
SH2 SH3 PTB PH
PI3K
Adaptor proteins (Grb2, Gab)
Cbl
Shp2
STATs
KinasesPhosphatases
Phospholipases
GTPase
Grb2 Docking proteins (IRS) IRS
PKB (AKT)
PDK1
RTK ligands: RTKs:
-insulin -EGF -PDGF -CSF1 -TGF -growth factors -EGFR -IR