11.3 Signal Transduction III

Question 1

Enzyme linked receptors

Answer 1

A type of cell-surface receptor where the binding of ligands to these receptors causes activation of enzymatic activity. They do not require Intermediate complexes like G proteins or second messengers.

Question 2

Enzyme linked receptors generally span the membrane how many times?

Answer 2

Once

Question 3

How many total types of classes of enzyme linked receptors are there?

Answer 3

6

Question 4

Receptor tyrosine kinases have a highly variable _______ domain and interact with a wide variety of ______.

Answer 4

Extracellular domain

Ligands

Question 5

What is the basic structure of the cytoplasmic side of the receptor tyrosine kinase molecule?

Answer 5

A conserved domain that has kinase activity which phosphorylates the amino acid tyrosine on some other protein

Question 6

Receptor tyrosine kinases receive signals that the cell uses to understand whether or not it should _______.

Answer 6

Grow and divide

Question 7

Mutations in receptor tyrosine kinase domains leads to

Answer 7

The cell always receiving a signal to grow. Important cause of uncontrolled growth in some types of cancers.

Question 8

When a ligand binds to a tyrosine kinase receptor, what initially happens?

Answer 8

The receptors form a dimer.

Question 9

Cross-phosphorylation

Answer 9

The kinase active region of the intracellular domain phosphorylates identical domains on the receptor that it is dimerized with (it does not phosphorylate itself)

Question 10

What happens when you introduce a mutated receptor protein that has a non-functional kinase domain to a receptor tyrosine kinase?

Answer 10

Dimers form but no phosphorylation or cross-phosphorylation occurs. This is a dominant negative effect because the mutant can prevent the activation of a normal receptor.

Question 11

The insulin tyrosine kinase receptor is a ________ structure.

Answer 11

Tetramer

Question 12

Insulin receptor substrate 1 (IRS1)

Answer 12

A coupling protein where the location of the phosphorylated docking sites are that are generated by ligand binding to the receptor

Question 13

IRS1 can serve as a ________ protein.

Answer 13

Scaffold protein by binding to phosphorylated phosphoinositides found in the cell membrane

Question 14

How do receptor tyrosine kinases act as scaffold proteins?

Answer 14

The multiple phosphorylated sites serve as docking sites for downstream signaling proteins

Question 15

Platelet derived growth factor (PDGF)

Answer 15

A receptor tyrosine kinase which is a single activated receptor but has docking sites for 3 different types of signaling molecules. This allows it to control a fairly wide variety of cellular events.

Question 16

SRC

Answer 16

The best known protein that interacts with the receptor tyrosine kinase docking sites. Contain SRC homology domains.

Question 17

SH2 and SH3

Answer 17

SRC homology domains that are used by signaling proteins to bind to phosphorylated tyrosines on receptor tyrosine kinases.

Question 18

What are the 2 receptor kinase signaling pathways that we focus on in this lecture?

Answer 18

1. Ras pathway

2. Pi-3K/AKT pathway

Question 19

G-protein Ras has how many domains?

Answer 19

One, it is monomeric

Question 20

Ras

Answer 20

A major Porto-oncogene : it is a normal protein that is often found to be mutated in cancer cells. It is a membrane associated G-protein.

Question 21

Ras is activated by ?

Answer 21

Not by receptors but instead by a series of other proteins beginning with an adapter protein containing SH2 and SH3 domains.

Question 22

SOS

Answer 22

In Ras signaling, SOS is recruited to the membrane and catalyzes the replacement of GDP on Ras with GTP

Question 23

Ras-GAP

Answer 23

GTPase activating protein for Ras to hydrolysis GTP to GDP

Question 24

MAPK pathway

Answer 24

Mitogen activated protein kinase pathway.

Ras activation initiates a cascade of signaling kinases which leads to phosphorylation of multiple downstream targets.

Question 25

Mitogen

Answer 25

Hormones that stimulate cell growth

Question 26

How does a cell specifically activate the MAPK pathway it wants?

Answer 26

By use of scaffold proteins that bring only the correct downstream signaling components together with their receptor.

Question 27

IGF

Answer 27

Insulin-like growth factors. Signaling molecules that activate the receptors of PKB/Art signaling pathways

Question 28

PIP3

Answer 28

Associated with the PKB/Akt pathway.... forms a membrane associated binding site for both Akt and PIP3 dependent kinase called PDK1.

Question 29

Many of the cytokines activate the _______ signaling pathway.

Answer 29

JAK STAT (A type of tyrosine kinase associated receptor signaling pathway) Dimerization of the receptor brings 2 JAX proteins close enough together that they cross-phosphorylate each other.

Question 30

STAT

Answer 30

Signal transducer and activators of transcription. Transcription factors.

Question 31

What happens when STAT binds to an activated receptor?

Answer 31

They're phosphorylated by JAK and then forms a dimer in the cytoplasm which creates an active transcription factor. The dimer is the transcription factor.

Question 32

What is a very direct way for a cell to alter gene expression patterns?

Answer 32

Using the JAX STAT pathway

Question 33

What key signaling proteins use the JAX STAT signaling pathway?

Answer 33

1. Interferons | 2. Growth factors: growth hormone and prolactin

Question 34

TGF-beta is a type of _________ receptor family?

Answer 34

Receptor serine/threonine kinase

Question 35

TGF-beta family regulates _____, _______, ______ and ________.

Answer 35

Pattern formation (development) Proliferation Cell death Extracellular matrix formation

Question 36

What is the structure of TGF-beta in its inactivated state?

Answer 36

Homodimers of type I and type II receptors

Question 37

What is the structure of TGF-beta in its activated state?

Answer 37

Tetramers

Question 38

Smad protein

Answer 38

A latent transcription factor that is recruited by Type I receptors on a TGF-beta domain, it gets phosphorylated and dissociate from the receptor complex and form an active dimer with another Smad in the cytoplasm. The dimer enters the nucleus and binds to the promoter of genes.

Question 39

Histidine-kinase associated receptor signaling pathway controls ________.

Answer 39

The movement of bacteria.

Question 40

How is flagella movement regulated?

Answer 40

Direction of rotation is regulated by a signaling system that when activated will cause some of the flagella to move in the opposite direction. This creates turbulence and results in tumbling. Downregulation of this signaling system returns the flagella to the correct direction of rotation.

Question 41

Methylation of the histidine-kinase associated receptor causes ?

Answer 41

Adaption/desensitization to a constant stimulant.

Question 42

What are 2 differences between G protein coupled receptors and enzyme linked receptors ?

Answer 42

1. G protein coupled receptors require an Intermediate complex. Enzyme linked receptors directly activate enzyme activity after a signal. 2. G protein coupled receptors contain 7 transmembrane pass proteins, enzyme linked receptors contain 1

Question 43

How does ligand binding lead to the production of an intracellular signal by receptor tyrosine kinases?

Answer 43

The production of an intracellular signal uses a process known as cross-phosphorylation. When a ligand binds to a receptor, the receptor forms a dimer. The kinase domain of the receptor then phosphorylate the same domain on the receptor it forms a dimer with.

Question 44

The active Akt protein does what?

Answer 44

Inhibits the process of cell death

Question 45

What are CheA, CheY and CheZ proteins?

Answer 45

Used in the signaling system used to control the movement of bacteria by controlling the rotation of the flagella.

Question 46

CheA

Answer 46

A histidine kinase that attaches to the receptor by use of the CheW adapter protein and phosphorylates itself. It then transfers PO4 to Asp on the target protein (CheY)

Question 47

CheY

Answer 47

With the use of energy, CheY is activated and binds to the flagella motor causing it to turn in the opposite direction, therefore the bacteria tumbles.

Question 48

CheZ

Answer 48

Shuts off the change in direction caused by CheA and CheY and the bacteria flagella returns to normal function

Question 49

What class of receptors regulates the movement of bacteria?

Answer 49

Histidine-kinase associated receptors