Barbieri

Question 1

Phenotypic and genotypic remodeling in basal signalosome

Answer 1

Phenotypic: 1. cell signaling via PTM 2. alteration in expression levels of individual signaling components

Genotypic: 1. mutations in signaling components

Question 2

Cell communication through electrical and chemical signaling mechanisms

Answer 2

1. gap junctions that communicate by passing electrical current
2. diffusion of second messengers - one cell releases stimulus/repressor which diffuses to target cell w/receptors

Question 3

General properties of cell signaling pathways

Answer 3

Stimuli act on cell-surface receptors

Transducers which use amplifiers to generate internal messengers that act locally or diffuse

Messengers that engage sensors coupled to effectors that activate cellular responses

Question 4

How cell stimuli are released from cells

Answer 4

1. membrane anchored stimuli released by ectoderm shedding

2. stimuli formed in cytoplasm are packaged into vesicles and released by exocytosis

Question 5

4 main modes of stimuli action

Answer 5

1. juxtacrine: membrane-anchored stimuli activate receptors on neighboring cells
2. autocrine: stimuli that are released activate receptors on same cell
3. paracrine: stimuli activate neighboring cells
4. endocrine: stimuli enter blood stream to act on distanced cells

Question 6

3 major mechanisms for cell signaling

Answer 6

1. receptor-tyrosine kinases
2. GPCRs
3. Channels

Question 7

Receptor Tyrosine Kinase- EGF example

Answer 7

EGF precursors located in PM that are cleaved by proteases (such as ADAM proteases). The growth factors then act on EGF receptors.

Question 8

GPCRs

Answer 8

Most neurotransmitters and hormones act through GPCRs. GPCRs have 3 subunits (alpha, beta, gamma) to stimulate amplifier such as adenylyl cyclase (AC) to generate cAMP or phospholipase C (PLC) to generate DAG IPsP3

Question 9

Ion channels as receptors for cell stimuli

Answer 9

Ion channels have all components of signaling pathway (receptor, transducer, and amplification).

Gating of Ca2+ ions changes membrane potential (V) which has a messenger function by altering activity of voltage-operated Ca2+ channels.

Question 10

Signal Transduction Methods

Answer 10

1. Preformed complexes
2. Diffusion of signaling elements
3. Post-translational modifications
4. Proteolytic cleavage

Question 11

Preformed complexes

Answer 11

Info is transferred from one signaling element to the next through conformational coupling.
EX: association of voltage-operated Ca2+ channels with the proteins responsible for exocytosis of synaptic vesicles

Question 12

Diffusion of signaling elements

Answer 12

1. 2nd messengers (Ca2+, cAMP, cGMP)
2. Proteins like extracellular signal regulated kinase 1/2 (ERK1/2)
3. activated transcription factors translocating to cytoplasm into nucleus

Question 13

Proteolytic cleavage

Answer 13

1. hormone precursors that activate peptides

2. protein degradation

Question 14

PTMs

Answer 14

PTM modulate component A, which then acts on component B to bring about a conformational change.

Include a host of modifications.

Question 15

Phosphoylation

Answer 15

• most common PTM
• occurs at serine, threonine, and tyrosine
• tyrosine phosphorylation heavily studied, prevalent in a lot of human disease via receptor tyrosine kinase

Question 16

Mechanism of phosphorylation

Answer 16

• Serine, threonine, and tyrosine have a nucleophilic (-OH) group that attacks the terminal phosphate group (-PO3) on an ATP donor. This transfers PO4 to aa side chain which is mediated by Mg2+
• Phosphorylation is reversible and regulates protein function

Question 17

Lipidation

Answer 17

targets proteins to membranes in organelles, vesicles, and the PM.

Question 18

4 types of lipidation

Answer 18

1. GPI anchor
2. N-terminal myristoylation
3. S-myristoylation
4. S-prenylation

Question 19

GPI anchor

Answer 19

Membrane bound proteins that function as enzymes to adhesion. They contribute to overall organization of membrane bound proteins, and mediate receptor-mediated signal transduction pathways.

Question 20

N-myristoylation

Answer 20

Method to give proteins a hydrophobic handle for membrane localization. However, this is not a permanent anchor.

Question 21

S-palmitoylation

Answer 21

Permanently anchors the protein to the membrane. This can be reversed by thioesterases though.

Question 22

S-prenylation

Answer 22

Adds a farnesyl or geranylgeranyl group and is hydrolytically stable

Question 23

Protein ubiquitination in cell signaling and protein degradation

Answer 23

Ub of a protein alters conformation enabling them to carry out various signaling functions in the control of cellular responses.

Ub also marks certain proteins for degradation by the proteasome.

Question 24

Proteolytic cleavage of hormone precursors

Answer 24

POMC (large polypeptide hormone precursor) cleaved into number of biologically active peptides that can act as hormones or neurotransmitters