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Test 4 Chapter 14
Receptor Class 4,5, & 6
113
Biology
Undergraduate 3
05/03/2015

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Term
Receptor Class 4: Receptors with Intrinsic or Associated Enzyme Activity has 3 subgroups, can you name them?
Definition
1. Intrinsic Ser/Thr Kinase Activity
2. Intrinsic Tyrosine Kinase Activity
3. Cytokine Receptors (assoc with enzymes)
Term
What do the receptors in subclass one do?
Definition
They phosphorylate serine and threonine residues on themselves or other proteins
Term
Name the first messengers for subgroup one....(there are 4)
Definition
BMPs, GDFs, Activins, and TGF-Beta
Term
What are the ancestral proteins that play fundamental roles in embryonic patterning?
Definition
BMPs
Term
Which first messenger, in subgroup one, regulates cartilage and skeletal development?
Definition
GDFs
Term
What regulates the release of pituitary hormones?
Definition
Activins
Term
Which first messenger, in subgroup one, regulates cell growth and morphogenesis and are a superfamily of ligands
Definition
TGF-Bs
Term
Which TGFB was first discovered, and what does it do?
Definition
TGFB-1
It was identified as a proliferation inhibitor in some tissues
Term
All of subgroup one's first messengers are what kind of dimers?
Definition
Homodimers
Term
What does a transforming factor do?
Definition
It induces cells into a proliferative state
Term
How many GDF's do each of these have:
Nematodes?
Fruit Flies?
Humans?
Definition
Nematodes: 6
Fruit Flies: 9
Humans: 42
Term
What term describes when one receptor driven pathway activates intermediates of other receptor driven pathways?
Definition
Crosstalk
Term
All the first messengers of subclass one are homodimers, what kind of bond usually holds them together?
Definition
Inter-chain Disulfide bond
Term
What is the representative receptor for subclass one?
Definition
TGFB-R
Term
Can you name the 3 subunits TGFB-R has?
Definition
Type RI....55 kDa
Type RII... 70-85 kDa
Type RIII.... 280 kDa
Term
Out of the 3 subunits of TGFB-R, which ones are glycoproteins with single membrane spanning domains?
Definition
RI and RII
Term
Out of the 3 subunits of TGFB-R, which ones have intrinsic ser/thr kinase domains in their C-terminal segment?
Definition
RI and RII
Term
Out of the 3 subunits of TGFB-R, which one has a constitutively active protein kinase domain that operates when linked up to RI?
Definition
RII
Term
Out of the 3 subunits of TGFB-R, which one will never have kinase activity?
Definition
RIII
Term
Out of the 3 subunits of TGFB-R, which one functions only as a co-activator and aiding in binding ligands to cell membranes?
Definition
RIII
Term
Out of the 3 subunits of TGFB-R, which one has a highly conserved region of ~30 amino acids that must be phosphorylated in order to become active?
Definition
RI
Term
The amino acid sequence found on the subunit RI has what kind of domain?
Definition
GS Domain
Term
TTSGSGSGLP corresponds to what?
Definition
GS Domain
Term
During receptor activation of Subgroup 1 the ligand binding at the cell membrane results in the dimerization of which two subunits? and what complex does this form?
Definition
RI and RII subunits

forms receptor ligand complex: TFGB-1-RI-RII
Term
Once the Receptor Ligand Complex is formed, the structure is phosphorylated at the GS Domain at the serine and threonine residues, which form what complex?
Definition
Active Receptor Complex
Term
C.elegans is known as what?
Definition
The Worm
Term
What is the scientific name for the fruit fly?
Definition
Drosophila melanogaster
Term
Which gene and which protein were used in the research done with the fruit fly?
Definition
The gene dpp, decapentaplegic

The protein MAD, work down stream from the dpp and its receptor
Term
While studying the worm what did they find that were similar to receptor ser/thr protein kinases, like TFGB-R?
Definition
daf 1 and daf 4
Term
What was also discovered while working with the worm that is homologous with mad (from the fly)?
Definition
Sma
Term
Now that MAD and Sma have been discovered as being homologous to each other, it was then realized that they were homologous to humans as well... what do we call them in humans?
Definition
smads
Term
Name the first messengers in subgroup 2 of class 4 receptors...(there are 5)
Definition
NGF
PDGF
FGF
EGF
Insulin
Term
What are the representative receptors of subgroup 2?
Definition
Any RTK, insulin receptors, growth factor receptor
Term
The process in which a molecule, such as a receptor, catalyzes phosphorylation of its own subunits is called?
Definition
Trans-Auto Phosphorylation
Term
What kind of domain does subgroup 2 have?
Definition
SH2 Domains
Term
What are SH2 domains?
Definition
They are specifically shaped domains that bind phosphorylated tyrosines and other proteins
Term
What serves as a docking site for molecules that have SH2 domains?
Definition
The phosphotyrosine residues in the cytosolic domains of activated RTKs
Term
What is an example of SH2 containing proteins?
Definition
GRB2
Term
GRB2 acts like a _____?____ and links other proteins to the activated receptor complex?
Definition
adaptor protein
Term
What do adaptor proteins not have?
Definition
They do not have intrinsic enzymatic activity
Term
Adaptor proteins serve as sites for what??
Definition
For accumulation of factors and enzymes
Term
GRB2 links with several proteins, name one example
Definition
SOS
Term
SOS was discovered in which animal
Definition
the fly
Term
SOS is what?
Definition
a RAS-GEF
Term
What does GEF do?
Definition
GTP exchange factor that promotes the release of GDP and replacement of GTP on RAS
Term
What is a archetype of a large (>70) superfamily of monomeric GTPases that are anchored at plasma membrane and at other membranes, some forms maybe free floating. Other members include: Rho, Rab, Ran, Arf
Definition
Ras
Term
What does Ras do?
Definition
regulates cell growth and differentiation
Term
What is Ras often referred to as, when it is mutant?
Definition
proto-ocogene
Term
What is it called when a gene that has a normal cellular function yet when mutant results in tumor formation (ocogenesis)?
Definition
Proto-ocogene
Term
What enchances the GTPase activity of the Ras superfamily?
Definition
Presence of Ras-GAPs
Term
What promotes cell division by binding on outside of cell?
Definition
Mitogen
Term
What was the first MAPK found?
Definition
p38 MAPK
Term
In the RTK pathway, subgroup 2's pathway, why is it such a long complicated pathway?
Definition
Because all the steps can be regulated, allows for fine tuning
Term
Cyclin and CDK do what?
Definition
Move the cell into the next stage of cell division
Term
What are the first messengers for subgroup 3 (cytokine receptors).... there are 5
Definition
Foreign antigens on T-cells
Interlukins
Immunoglobulins
Epo
Hormones
Term
What does Epo do?
Definition
promotes RBC division
Term
Subgroup 3, Cytokine receptors, have no intrinsic catalytic activity therefore they must recruit cytosolic kinases termed?
Definition
nrPTK
non-receptor protein tyrosine kinases
Term
nrPTKs are a large group of signaling proteins, what do they do?
Definition
they control cell proliferation, differentiation and death
Term
Name the two ways nrPTKs can bind to their domains
Definition
Some nrPTKs have unique N-termini with added fatty acids to target them to membranes

Other nrPTKs are targeted to sites of action through by their SH2 domains, binding phosphotyrosine residues on receptors
Term
What is involved in detection of foreign antigens when present with the MHC
Definition
TCR T cell receptors aka T-Lymphocyte receptor
Term
What is the first line of defense against infection by microorganisms
Definition
B-lymphocyte receptor
Term
Which cytokine, when secreted by a T-helper cell enhances the proliferation of activated T and B cells and increases the cytolytic activity of NK cells and secretion of IgG
Definition
Interleukin 2 receptor
Term
What is present on mast cells and basophils that play an important role in hypersensitivity and the initiation of acute inflammatory responses?
Definition
Immunoglobulin receptors
Term
Give an example of an immunoglobulin receptors
Definition
IgE, IgG, IgA
Term
What binds Epo at an important final stage of maturation of erythroid cells into mature red blood cells
Definition
Epo receptors
Term
What has been used by athletes to improve their performance
Definition
Erythropoietin
Term
What binds the pituitary hormone prolactin which plays a pivotal role in the regulation of lactation
Definition
Prolactin receptors
Term
Binding interferons to their respective receptors (IFNAR and IFNGR) activates what?
Definition
JAKs
Term
STAT transcription factors have 3 domains, can you name them
Definition
SH2 domains on N-terminus
Central DNA binding domains
C-terminal tyrosine that can be phsohporylated
Term
What allows STATs to dimerize?
Definition
SH2 domain
Term
What does NLS stand for?
Definition
Nuclear Localization Signal or Sequence
Term
Which receptor class has receptors that relay signals via cytoplasmic heterotrimeric G-proteins
Definition
Receptor Class 5: G-protein coupled receptors
Term
Name the first messengers for Receptor Class 5....there are 5 and give examples of each
Definition
Biogenic Amines: nonadrenaline, dopamine, 5HT, Acetylcholine

Amino acids and ions: glutamate, Ca 2+, GABA

Lipids: prostaglandins, leukotrienes

Peptides: Chemokines, angtiotensin, thrombin

Others: light, odorants, nucleotides
Term
What is the representative receptors for receptor class 5?
Definition
7TM
Term
What makes a 7TM?
Definition
When 3 exposed loops are on each side of membrane, the N terminus projects outside the cell and the C-terminus is cytosolic
Term
In receptor class 5, ligand binding alters the conformation of which loop?
Definition
C3 loop
Term
After the conformational change in the C3 loop, the loop is then able to bind and activate a ____?
Definition
GTP-binding protein
Term
GTP-binding proteins includes which two things?
Definition
G-proteins and GTPases
Term
What do GTPases do?
Definition
hydrolyze GTP to GDP
Term
The term G-protein is reserved for what?
Definition
GTP-binding proteins that interact with 7TM rececptors
Term
The G-protein is composed of 3 subunits, name them..
Definition
Aplha, Beta, and Gamma
Term
Why do we call G-proteins heterotrimeric proteins?
Definition
because they are made up of 3 subunits
Term
Which receptor class takes up as much as 5% of the mammalian genome?
Definition
Receptor class 5: G-protein coupled receptors
Term
How many genes, out of the alpha subunits of g proteins are expressed in most animals cells?
Definition
9-10
Term
Which G-protein subunit begins and ends the signaling cycle with GDP situated in the nucleotide binding site
Definition
Alpha
Term
GTP bound to an alpha subunit does not last long, why?
Definition
Within seconds the alpha subunit catalyzes GTP to GDP aided by RGS proteins
Term
Which disease is an example of when ADP-ribosylation of the G protein alpha subunit complex allows to continually activate adenylyl cyclase?
Definition
Cholera
Term
What activates effector enzymes?
Definition
They are activated by the GTP binding alpha subunits of G proteins
Term
What do effector enzymes do?
Definition
They will catalyze formation of second messengers
Term
Name three examples of effector enzymes
Definition
Adenylyl cyclase and guanylyl cyclase
Phospholipase C
Calmodulin
Term
Which effector enzyme catalyzes the formation of cAMP from ATP?
Definition
Adenylyl cyclase
Term
What is best known for the breakdown of liver glycogen?
Definition
cAMP
Term
What is activated when cAMP levels rise in the cell?
Definition
PKA
Term
Phophorylation by PKA is a classic example of which type of feedback?
Definition
Negative feedback mechanism
Term
What do phospholipases do?
Definition
the generate various second messengers
Term
Where can inositol be found?
Definition
inner leaflet
Term
What is the substrate for the formation of prostaglandins and leukotrienes?
Definition
Arachidonate
Term
What do SOCs do?
Definition
they open and allow Ca 2+ to rush into the cell
Term
Many calcium effects are mediated by what?
Definition
Calmodulin
Term
What does Calmodulin bind?
Definition
$ Ca2+ ions in positive cooperation
Term
Active Calmodulin is an intermediate player in the production of what
Definition
Nirtic Oxide NO
Term
There is a huge list of important physiologic pathways.... name some of them
Definition
I am going to list the easy ones to remember...there are lots more.

Initiation of mitochondria biogenesis
Inhibition of NFkB
Regulation of the cell cycle
Initiation and inhibition of apoptosis
Antimicrobal Effects
Term
LIst the second messengers in Receptor class 5
Definition
cAMP
cGMP
DAG
IP3
Term
What do second messengers interact with?
Definition
a specific set of downstream kinases or phosphatases, either directly or indirectly, to cause phosphorylation or dephosphorylation of target protein domains
Term
What is another name for the Teddy bear protein
Definition
Calmodulin
Term
[image]
Definition
cAMP
Term
[image]
Definition
IP3
Term
[image]
Definition
cGMP
Term
Which receptor class has the Wnt/Frizzled pathway?
Definition
Receptor class 6
Term
Which family of first messengers is cysteine rich glycoproteins that act in both short and long range signaling
Definition
Wnt
Term
How many family members of wnt can be found in vertebrates
Definition
19
Term
Regulation of body axes polarity and limb formation in developing embryos is done by the binding of what?
Definition
Wnt
Term
Wnt can also do what to stem cells?
Definition
Proliferate them
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