Enzyme-linked cell surface receptors

Question 1

Receptor Classes - 6

What are they and what are their receptors?

Answer 1

Receptor guanylyl cyclases - ANP receptor; Receptor tyrosine kinases - growth factor receptors, insulin receptor, RAS; Tyrosin kinase associated receptors - erythropoietin receptor; Receptor Tyrosine phosphatases - CD45; Receptor serine/threonine kinases - Mullerian inhibiting substance; bone morphogenic protein

Question 2

What is the ANP receptor?

Answer 2

a single membrane spanning protein with an extracellular receptor binding domain, a transmembrane domain and an intracellular guanylyl cyclase domains.

Question 3

When is the guanylyl cyclase inactive?

Answer 3

As an unbound monomer

Question 4

Guanylyl cyclase catalyzes what reaction?

Answer 4

The generation of cGMP from GTP and cGMP activates protein kinase G
s;o GTP > cGMP > protein kinase G > targeted proteins phosphorylated

Question 5

What does Protein kinase G phosphorylate?

Answer 5

Target proteins

Question 6

What do phosphorylated proteins mediate?

Answer 6

hormone function

Question 7

BP Regulation - Why is ANP released from secretory vesicles in atria?

Answer 7

In response to an increase in stretch.

Question 8

BP regulation - Where are NP-A/B receptors present?

Answer 8

adrenal glands, kidneys, and in vascular smooth muscle.

Question 9

BP Regulation - what is caused by activation of NP-A/B?

Answer 9

results in cGMP generation and PKG activation.

Question 10

BP Regulation - NP - A/B activation in the kidney increases? Reduces? Inhibits?

Answer 10

Increases glomerular filtration, reduces renin secretion, and inhibits Na+ and water retention.

Question 11

BP Regulation - NP-A/B activation in adrenal gland inhibits? What does inhabitation lead to?

Answer 11

Inhibits aldosterone secretion, which leads to reduction of Na+ in water retention

Question 12

BP Regulation - NP-A/B in blood vessels causes?

Answer 12

vasodilation via a relaxation of smooth muscle.

Question 13

BP Regulation - Reduction in blood volume and vasodilation lead to what?

Answer 13

Reduction in BP

Question 14

Insulin receptors consist of two what? What do they contain?

Answer 14

The receptor consists of two extracellular subunits which contains hormone binding domains and two membrane spanning subunits which contain cystolic tyrosine kinase domains.

Question 15

What does binding of insulin cause?

Answer 15

activation of the receptor through auto-phosphorylation of cytosolic tyrosine kinase

Question 16

Activated insulin receptor pathways - 1 - IRS1 pathway
where?
activated receptor associated with what? What does that cause?

Answer 16

In skeletal muscle and adipose tissues.

Activated receptor associates with IRS-1 on adapter protein, and causes activation of PI3K.

Question 17

What does PI3K mediate?

Answer 17

mediates fusion to the cell membrane of vesicles that include GLUT4 in the vesicle membrane

Question 18

What does GLUT4 mediate?

Answer 18

facilitated diffusion of glucose into the cell.

Question 19

Insulin receptor signaling - MAPK pathways: The activated receptor activates what?

Answer 19

Activated receptor activates the adapter protein SOS

Question 20

SOS activates what? and by promoting what? In the insulin pathways.

Answer 20

RAS by promoting the GTP bound form

Question 21

What does RAS-GTP activate?

Answer 21

Activates the MAP-kinase pathway.

Question 22

What does activation of MAPK consist of?

Answer 22

Phosphorylation of MAPKKK and then MAPKK and then MAPK

Question 23

What does phosphorylate MAPK translocates what?

Answer 23

translocates into the nucleus and activates transcription of early genes.

Question 24

What do jun and fos proteins do in insulin receptor?

Answer 24

translocate into the nucleus and activate the transcription of secondary genes, such as GLUT4 and GLUT1

Question 25

What family does RAS belong to and what are they involved in?

Answer 25

RAS belongs to monomeric GTPases, involved in relaying signals within the cells to the nucleus, cytoplasm, secretory machinery

Question 26

When RAS binds GTP it is? When RAS is bound to GSP it is.. | What is RAS intrinsic GTPase enhanced by?

Answer 26

switched on switched off accessory proteins

Question 27

What is MAPK signaling involved in?

Answer 27

part of a pathway that leads to cell proliferation.

Question 28

What does mutated RAS lack? What does this lead to?

Answer 28

lacks GTPase activity, fails to allow signal termination and causes excessive cell proliferation leading to cancer. Ras is called proto-oncogene

Question 29

Insulin deficient diabetes mellitus: | What are the signs and hows it treated?

Answer 29

high blood glucose, defective pancreatic Beta cells, insufficient insulin secretion, low insulin levels, treated with insulin.

Question 30

Insulin Resistant Diabetes Melliktus

Answer 30

High blood glucose, defective insulin receptor/signaling in peripheral tissues; insulin resistance at various levels, normal or high plasma insulin levels; treated with insulin.

Question 31

Diabetes mellitus presentation, pathology, and Plasma glucose levels?

Answer 31

Presentation - weight loss, polydipsia/polyuria/weakness. Pathology - hypoglycemia, glucosuria/hyperlipidemia, ketonuria, uremia. Plasma glucose = 22-44 mM

Question 32

Failure to uptake glucose results in?

Answer 32

hypoglycemia > exceed renal threshold > glucosuria Hyperosmotic plasma > dehydration of cells > hyperglycemic coma Polydipsia > osmotic diuresis > polyuria

Question 33

Intracellular energy shortage results in..

Answer 33

Mobilization of fatty acids > hyperlipidemia. Metabolism of fatty acids > acetyl-CoA >acetoacetate > 4-OH butyrate + acetone. Metabolism of fatty acids > keto acidosis > acidotic coma. Metabolism of fatty acids > ketonuria. AA metabolism > urea production > uremia.

Question 34

Erythropoietin receptor consists of...

Answer 34

single membrane spanning protein with an extracellular hormone binding domain. The cytosolic domain does not have tyrosine-kinase activity.

Question 35

Binding of erythropoietin results in..

Answer 35

dimerization of the receptor and the binding of a non-receptor tyrosine-kinase (JAK2)

Question 36

JAK2 bound to receptor does what?

Answer 36

phosphorylates/activates STAT5

Question 37

What does JAK2 do?

Answer 37

phosphorylates itself as well as the receptor

Question 38

Erythropoietin Receptor Signaling: JAK2/STAT pathway -

Answer 38

The activated receptor/tyrosine kinase complex phosphorylates/activates STAT5

Question 39

What does STAT5 do?

Answer 39

translocates into the nucleus and activates transcription of genes, prevents apoptosis.

Question 40

Erythropoietin Receptor signaling - MAPK pathway, what does RAS-GTP activate and how?

Answer 40

the MAPK pathways by mitogen-activated protein kinase

Question 41

Erythropoietin Receptor signaling - MAPK pathway; what do jun and fos do?

Answer 41

translocate into the nucleus and activate the transcription of secondary genes such as cyclin D

Question 42

What is cyclin D necessary for?

Answer 42

cell division

Question 43

What is Erythropoietin produced by and how is production stiulated?

Answer 43

Produced by the kidney; production stimulated by a reduction of oxygen partial pressure

Question 44

What does EPO increase and how?

Answer 44

the number of erythrocytes by stimulated proliferation of erythrocyte progenitor cells in bone marrow.

Question 45

A failing kidney may not be able to produce...

Answer 45

a sufficient amount of EPO

Question 46

How are low levels of endogenous EPO treated?

Answer 46

giving recombinant human EPO, rhEPO can improve status of animal by boosting oxygen delivery to tissues.

Question 47

Side effects of EPO misuse

Answer 47

increase in RBC increases blood velocity and poses risk of embolism

Question 48

Some cell surface receptors are linked to or associated with _____. What are the 3 examples?

Answer 48

enzymes; clyclases, kinases, phosphatases

Question 49

What two receptors exhibit intrinsic tyrosine kinase activity with agonist binding?

Answer 49

cell growth factor receptors and insulin receptors

Question 50

How is blood volume and pressure regulated? Via what two compounds? What is the name of the system?

Answer 50

Atrial natriuretic peptide, via cGMP and dPKG work with the renin-angiotensin-aldosterone system.