Introduction to Cell Signaling

Question 1

Outline the way cells communicate, starting with the release of ligand and ending with the termination of signaling

Answer 1

1) Signal could be ligand, light, heat, etc
2) binds to receptor
3) signal transduction which often includes kinases GTPase switch proteins and secondary messengers
4) protein structure is altered and/or DNA transcription is altered
5) terminate signaling

Question 2

Define autocrine signaling and give an example

Answer 2

cell releases hormone and binds to a receptor on itself

ex) hematopoeisis

Question 3

Define paracrine signaling and give an example

Answer 3

one cell produces hormone and a nearby cell recieves

ex) neuromuscular junction

Question 4

Define endocrine signaling and give an example

Answer 4

hormone is made by some cells and then released into blood stream for circulation
ex) insulin

Question 5

Describe the four general classes of signaling molecules used in the body

Answer 5

• amines: derived from arginine, phenylalanine, tyrosine, and tryptophan (hydrophilic)
• peptides and proteins: all pituitary hormones, insulin, glucagon
• steroid hormones: hydrophobic
• small molecules: amino acids, Ca2+, nitric oxide

Question 6

Describe examples of how two different ligands may have the same physiological impact on a tissue

Answer 6

Attach to different receptors (or subtypes) that have the same effect on the cell (ex. activate cAMP) and therefore have the same impact

Question 7

Describe examples of how a single ligand can have a very different physiological effect, depending on cell type

Answer 7

1 ligand may have 2 different receptors it can bind to and will produce different effects
ex) nicatinic (stimulatory) vs muscarinic (inhibitory) ACTH receptors

Question 8

Outline the four general types of receptors utilized by cells, including a brief description of their mechanism of action

Answer 8

1) GPCR
2) Ligand-gated ion channels
3) receptors with enzymatic activity
4) intracellular receptors

Question 9

Outline the structure and functions of GPCR in the physiology of humans

Answer 9

• 7 transmembrane sections of GPCR
• trimeric (alpha, beta, gamma) G-proteins
• alpha and gamma are bound to the membrane (beta held between)
• when trimeric G-protein bound to GPCR, triggers dissociation of subunits; alpha loses GDP & gains GTP; beta and gamma activated by not being attached to alpha
• alpha binds to target protein (effector protein)…cascade…

Question 10

Compare the activities of different types of G-alpha subunits

Answer 10

• alpha-s: stimulatory (stimulates adenylyl cyclase)
• alpha-i: inhibitory (inhibits adenylyl cyclase)
• alpha-t: transducin (activates PDE –> breaks down cGMP and therefore closes dependent channels)
• alpha-q: activates PLC (cleaves PIP2 to DAG and IP3)

Question 11

Compare the activation and activities of protein kinase A (PKA), protein kinase C (PKC), and phospholipase C (PLC)

Answer 11

PKA: activated by cAMP; travels to nucleus, regulate cytosolic enzymes
PKC: activated by DAG; lots of activities, transcription factor
PLC: activated by G-alpha-q, but in some isomers can be activated by beta and gamma; breaks PIP2 into DAG and IP3

Question 12

List the various types of membrane receptors with enzymatic activity

Answer 12

RTKs, Receptor Serine/Threonine Receptors, Tyrosine Kinase Associated Receptors (Cytokine)

Question 13

Compare the general RTK and cytokine receptor signaling pathways

Answer 13

RTK: ligand causes dimerization, phosphorylate one another, SH2 domain binds with adaptor protein (GRB2); guanine nucleotide exchange factor (SOS) is drawn to the membrane via adaptor protein; releases GDP from Ras; cascade of kinases; modulate transcription or alter protein
Cytokine (no intrinsic kinase activity): bind ligand; JAKs get phosphorylated; JAKs phosphorylate the dimer tails (tyrosine residues); STAT will bind; JAK phosphorylates STAT; release STAT and bind another; 2 STATs form dimer; travel to nucleus to activate transcription

Question 14

Describe general mechanisms whereby cell signaling pathways are attenuated/terminated

Answer 14

• cAMP is constantly broken down by phosphodiesterase which means once adenylyl cyclase stops, cAMP levels drop quickly
• phosphatases remove phosphates added by PKA
• BARK (beta-adronergic receptor kinase) is phosphorylated by PKA –> becomes activated and phosphorylates beta-adrenergic receptor which allows beta arrestin to bind and shut down the receptor

Question 15

Outline the general mechanisms utilized in signaling pathways that alter gene expression

Answer 15

• cAMP can regulate using PKA, CREB, and CRE
• RTKs regulate via MAPK-based phosphorylation of transcription factors
• STAT proteins
• for steroid hormones, intracellular receptor is transcription factor

Question 16

Explain what is meant by signal amplification as it relates to cell-signaling

Answer 16

one ligand can activate multiple g-proteins and each g-protein can activate many molecules and so on