laminas examen 2

8/12/2019 laminas examen 2

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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

laminas examen 2

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