1.1 Receptors and Signalling

Question 1

What are the three main extracellular signals?

Answer 1

Hormones - released by cells of one tissue, carried to new site of action for a specific response

Growth factors - regulate cell growth and differetiation

Cytokines - peptide molecules with local effects

Question 2

What are the two main intracellular signals?

Answer 2

Gases - diffuse across membrane to cause a direct effect

Steroids - bind to specific receptors in cell to activate it (transactivator), to regulate gene expression

Question 3

What are the tree major classes or cell surface receptors?

Answer 3

Ion channel linked receptor

G-protein coupled receptors (GCPRs)

Enzyme linked receptors

Question 4

What is an ion channel linked receptor and how does it work?

Answer 4

A channel in the plasma membrane

Ligand binds, confirmational change to allow diffusion down a conc. gradient

Question 5

What is a GCPR and how does it work?

Answer 5

A 7 pass trimeric G protein (𝛂,𝛃,𝛄 subunits)

GDP -> GTP (at 𝛂 sub-unit) activates subunit = dissociation from other subunits (confirmational change) that activates an effector

Question 6

Explain signal transuction via secondary messenger cAMP

Answer 6

Free 𝛂 subunit (stimulatory) interacts with adenylyl lcyclase for ATP -> cAMP = rapid increase [2nd messanger]

cAMP activates PKA which phosphorylates protein substrates to affect cell’s function

Question 7

GCPRs havr a short signal duration due to…

Answer 7

G-protein activation is short (intrinsic GTPase activity converts GTP to GDP, reforming the inactive tri-subunit)

cAMP is readily broken down

Phosphatases rapidly reverses the effects of PKA

Receptor becomes desensitised to further sensitisation

Ligand is destroyed

Question 8

What does 𝛂-Gq do?

Answer 8

Activates phospholipase C

Causes PI turnover

Opens IP gates Ca2+ release channels

Question 9

How can Calcium concentrated by rapidly released?

Answer 9

Voltage gated channels

IP3 channels

Ryanodine receptors

Question 10

What is Calmodulin?

Answer 10

A multi-purpose intraceelular Ca2+ receptor,a cting as a switch to alter activity of other proteins such as myosin kinase

Question 11

What are Recpetor Tyrosine Kinases (RTKs)?

Answer 11

Single pass transmembrane proteins

Phosphoralate on tyrosin residues

Signalling cascase initiated by ligand-induced dimerisation of receptors

Question 12

Explain RTKs signalling transduction

Answer 12

RTKs activate PLC𝛄 and Ras

Signal from Ras carried forward by mitogen-activated protein kinase (MAPK) cascade (MAPKKK > MAPKK > MAPK> proliferation)