Cell Biology Chapter 23: Enzyme coupled receptors (Exam 3)

When a ligand binds to a receptor this leads to what:

Dimerization and autophosphorylation on tyrosines

Phosphorylated tyrosine residues provide _____ ______ for proteins with SH2 domains

Binding sites

Phospholipase-C gamma binds to:

• phosphotyrosine residues using their SH2 domains and becomes active

• PLC-gamma PIP2 to produce IP3 and DAG

Only activation of receptor tyrosine kinases by growth factors is:

Mitogenic

Receptor tyrosine kinases activate MAPs kinases which stand for:

mitogen activated protein kinases

The adaptor protein Grb2 binds to ___________ residues using what domain?

• Binds to phosphotyrosine residues using its SH2 domain

Grb2 uses its SH3 domain to bind to ______-rich regions on something called _____. The ___ is a GEF for a g-protein called Ras.

• proline-rich regions

• Sos

Ras-GTP activates the protein kinase ____. This protein ____ then phosphorylates MEK to activate it.

RAF

When MEK has been phosphorylated by RAF to become activated, it then phosphorylates ____ kinase to activate this protein.

MAP kinase

_____ kinase phosphorylates transcription factors which _____ expression of the immediately early response genes.

MAP kinase; increases

Explain the mechanism of receptor tyrosine kinases when activated mitogen activated protein kinases (MAPs Kinases):

1. The adaptor protein Grb2 binds to phosphotyrosine residues using its SH2 domain.

2. Then, Grb2 uses its SH3 domain to then bind to proline-rich regions on Sos.

3. Sos is then brought out pass the membrane to then bind to its G protein to become a GEF. It drops GDP to then bind to GTP. Sos is the GEF for RAS (activating this G-protein)

4. Ras-GTP activates the protein kinase RAF

5. RAF then phosphorylates MEK to become activated

6. MEK then phosphorylates MAP kinase to become activated

7. MAP kinase then can phosphorylate transcription factors which increases expression of the immediate early response genes

Yeast can exist as _____ or ______

Haploid or diploid

The immediate early response of genes can get transcribed first and transiently in response to:

• Growth factor stimulation

• C-fos, c-jun, c-myc are examples of transcription factors

The _____ _______ then increase the transcription of genes to make the proteins necessary for cell cycle progression like DNA synthesis, mitosis, and cytokinesis.

Transcription factors

(c-myc can start the binding in promoter region of genes)

MAP kinase phosphorylates _______ ______ which movie into the nucleus for immediate early response genes for cell division

Transcription factors

They are two sexes within yeast:

a and α

Haploids cells of the opposite sex can fuse to become diploid by:

Mating

Mating pheromones released by one cell type that binds receptors on the opposite cell type leading to ______

Mating

Yeast use a version of the ____ _______ pathway to respond to mating pheromones.

MAP kinase

A _______ _____ organizes each of the enzymes to ensure efficiency of the signaling pathway. This can allow for a cascade to take place.

Scaffolding protein

What’s the characteristics of insulin?

it tells cells to store glycogen

• it secreted by β-subunits on the pancreas to lower blood sugar levels

• The increase the metabolism of glucose

What’s insulin signaling?

1. The insulin receptor is a tyrosine kinase. The insulin receptor acts like a dimmer when not bounded.

2. This recruits and phosphorylates a scaffolding protein, Insulin Receptor Substrate 1 (IRS-1)

3. Grb2 binds photophotyrosine residues on IRS-1 leading to activation of the MAP kinase pathway

While this may account for some of the mitogenic effects of insulin, it is not truly a ____ _____ and this pathway has no effect on glucose uptake

growth factor

What’s the characterisitcs of phosphoinositide 3-kinase?

1. IRS-1 is also bound by PI-3 kinase via its SH2 domain

2. PI 3-Kinase phosphorylates phosphatidylinositol 4, 5 bisphosphate (PIP2) on the third carbon to produce phosphatidylinositol 3,4,5 trisphosphate (PIP3)

What does Phosphoinositide 3-kinase do?

It puts phosphate group on carbon 3 which is the phosphatidylinositol

PIP3 provides ____ ______ for proteins with a plekstrin homologous domain.

Binding sites

PDK known as phosphoinositide dependent kinase is dependent on the:

Binding on Phosphatidylinositol to become activated

Akt (protein kinase B) can get phosphorylated by:

PDK

Both PDK and it’s substrate Akt (protein kinase B) bind near each other at the _________ _______

Plasma membrane

PDK phosphorylates and activates _____

Akt (PKB)

Akt (PKB) phosphorylates multiple proteins leading to the translocation of vesicles containing:

Glucose transport proteins to the plasma membrane leading to glucose uptake

Akt (PKB) also phosphorylates proteins leading to the increased:

glycogen synthesis

What’s the process of glucose uptake?

1. Vesicles have these glucose travel across the plasma membrane through glucose transport proteins

2. This is going to turn on cells that synthesize glycogen

3. This will undergo exocytosis to then transport glucose outside the cell

How can PKA inhibit glycogen synthase?

1. cAMP binds to and activates protein kinase A

2. Protein kinase A then phosphorylates Phosphorylase Kinase activating it

3. Active phosphorylase kinase will then phosphorylate phosphorylase b→phosphorylase a, activating that enzyme

4. Phosphorylase A catalyzes cleavage of a terminal glucose from glycogen as glucose-1-phosphate

How can Akt inhibits inhibition of glycogen synthase?

1. Glycogen synthase is activated when it’s dephosphorylated

2. Glycogen synthase is inactive with phosphorylated

3. Glycogen synthase kinase inactivates glycogen synthase kinase (it’s always on when insulin is being secreted)

4. Akt can become active from the phosphorylation of ATP

Focal adhesions and FAK:

• have integrins that bind extracellular matrix and recruit focal adhesion kinase (FAK)

Cross-phosphorylation provides binding sites for ____

Src

__ is a soluble tyrosine kinase that phosphorylates additional tyrosines on FAK. It provides binding sites for PI-3 kinase, PLC-γ, and Grb2

Src

When Src provides the binding sites for PI-3 kinase, PLC-γ, Grb2 it:

Activates pathways that overlap with those activated by growth factors

Signaling leads to:

1. Growth and survival

FAK and Src family members are overactive and over expressed in multiple cancers

2. Development and migration

Regulates Rho, Rac, and Cdc42 to modify actin polymerization and organizatio

Serine and threonine kinases transform growth factor-b as it binds to a receptor that’s composed of 2 proteins:

2 type I

2 Type II

Following ligand binding, Type _____ receptors phosphorylate Type __ receptors to activate them

Type 2, Tyoe 1

An activated receptor is a serine/threonine kinase. It can phosphorylate ____ transcription factors.

Smad which regulates specific genes

Most serine/threonine kinases inhibits growth of most cell types and promotes tissue maturation by promoting:

Synthesis of extracellular matrix components

After bind TGF-β. The type 2 receptor kinase phosphorylates and activates type q receptor kinase which then activates a:

Signaling cascade