BCHM 210 Study Guide - Midterm Guide: Receptor Tyrosine Kinase, Irs1, Insulin Receptor

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31 Jan 2019

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This is a summary slide with the insulin bound to the alpha-subunit of the insulin receptor this leads to the cross-phosphorylation of the beta- subunits now its active; once its active, other tyrosine residues can get phosphorylated. Due the phosphorylation of tyrosine residues on the beta-subunit, you have an insulin receptor substrate-1 (irs-1) that binds to the phosphorylated tyrosine residue on the b-subunit. Irs-1 has a sh3-domain that binds to the regulatory domain of phosphoinositide 3-kinase. This phosphoinositide 3-kinase then phosphorylates pip2 to pip3: pip3 binds to pdk1 (pip3-dependent protein kinase) this activates pdk1, then akt gets phosphorylated by pdk1 (using atp) and now you have an activated. The activated pdk1 phosphorylates and activates akt, another protein kinase. Irs-1 and irs-2 are homologous and have a pleckstrin homology domain (helps bind to membrane) and phosphotyrosine binding domain; the phosphotyrosine binding domain helps it anchor itself to the beta-subunit of the insulin receptor.

Related Questions

The binding of platelet derived growth factor (PDGF) to the PDGF receptor stimulates phosphorylation of 8 tyrosines in the receptor's cytoplasmic domain. The enzyme phosphatidylinositol 3'kinase (PI 3-kinase) binds to one or more of the phophotyrosines through its SH2 domains and is thereby activated. To identify the activation phosphotyrosines, you synthesize 8 pentapetides that contain the critical tyrosines (at the N-terninus) in their phosphorylated or unphosphorylated forms. You then mix an excess of each of the various pentapeptides with phosphorylated PDGF receptor and PI 3-kinase. Immunoprecipitation of the PDGF receptor will bring down any bound PI 3-kinase, which can be assayed by its ability to add 32P-phosphate to its substrate.

A) Draw a flow diagram showing how this assay works.

B) Do your results support the notion that PI-kinase binds to phosphotyrosines in the activated PDGF receptor? Why or why not?

C) THe amino acid sequences of the PDGF receptor pentapeptide tested above (number accodingly to the position of tyrosine in the PDGF receptor) and peptide segments that are known to bind to PI 3-kinase in other activated receptors are shown below. Which amino acid residues are most important and why?

684 YSNAL YMMMR (FGF receptor)

708 YMDMS YTHMN (insulin receptor)

719 YVPML YEVML (hepatocyte growth factor receptor)

731 YADIE YMDMK (steel factor receptor)

739 YMAPY YVEMR (CSF-1 receptor)

743 YDNYE

746 YEPSA

755 YRATL

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33 Different glycoproteins can have a diverse array of oligosaccharides. Which of the statements below for making glycoproteins on plasma membrane is true?

(a) Extensive modification of oligosaccharides occurs in the extracellular space.

(b) Initial oligosaccharide chains are made by addition of one sugar at a time onto the protein in the ER lumen.

(c) Each layer of Golgi membrane structures contains identical modification enzymes for modifying sugar chain on proteins.

(d) ER lipids can be modified by sugar chain, which can be used for sugar chain modification of the proteins.

34 In a multicellular organism, when a signal needs to be sent to most cells the signal most suited for this is a ___________.

(a) neurotransmitter.

(b) hormone.

(d) plasma membrane anchored ligands.

35 Typically, members of the steroid hormone receptor family __________________.

(a) are cell-surface receptors.

(b) do not undergo conformational changes by binding to their ligands.

(d) interact with signal molecules that diffuse through the plasma membrane

36 Which of the following statements about what happens when a G-protein-coupled receptor activates a hetero trimeric G protein is true?

(a) The Î² subunit exchanges its bound GDP for GTP.

(b) The GDP bound to the Î± subunit is phosphorylated to form bound GTP.

(d) It activates the Î± subunit and inactivates the Î²Î³ complex

37 Which of the following statements about signal transduction is false

(a) Ca2+ concentration in cytosol will increase when PLC (Phospholipase C) is activated by signal.

(b) Cyclic GMP is made in smooth muscle cells when they received NO signal.

(d) Ligand binding to RTK activates its enzyme activity then the activated RTK phosphorylates tyrosine residues on itself.

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QUESTION 1

Which of the following is an example of an extracellular signal molecule?

	a.	IP₃
	b.	cAMP
	c.	Insulin
	d.	Diacylglycerol

2 points

QUESTION 2

Nuclear hormone receptors _____

	a.	Bind to water soluble ligands
	b.	Activate second messengers
	c.	Regulate transcription in response to ligand binding
	d.	Are normally located on the plasma membrane

2 points

QUESTION 3

Which of the following does not occur when a receptor tyrosine kinase is bound by ligand?

	a.	Phosphorylation of the RTK
	b.	Cytoplasmic proteins bind the phosphorylated RTK
	c.	Dimerization of the RTK
	d.	The RTK binds to DNA to regulate transcription

2 points

QUESTION 4

Which of these is a logical signal-transduction pathway?

	a.	An intracellular receptor activates phospholipase C, which cleaves a membrane protein to form IP₃, which then activates the opening of an ER channel protein, which releases cyclic AMP into the cytoplasm, where it binds to an intracellular enzyme that carries out a response.
	b.	A G-protein-linked receptor activates G protein, which activates phospholipase C, which cleaves a membrane lipid to form IP₃, which binds to a calcium channel on the ER, which opens to release calcium ions into the cytoplasm, which bind to an intracellular enzyme that carries out a response.
	c.	An ion-channel receptor opens, allowing a steroid hormone to enter the cell; the steroid hormone then activates protein kinases that convert GTP to GDP, which binds to an intracellular enzyme that carries out a response.
	d.	A tyrosine-kinase receptor activates adenylyl cyclase, which activates phospholipase C, which converts ATP into cyclic AMP, which binds to an intracellular enzyme that carries out a response.

2 points

QUESTION 5

Which of the following is an example of signal amplification?

	a.	activation of an enzyme molecule
	b.	activation of a specific gene by a growth factor
	c.	Breakdown of many cAMP molecules
	d.	activation of 100 molecules by a single signal binding event

2 points

QUESTION 6

Consider a signal transduction pathway that utilizes cAMP as a second messenger to activate PKA (Protein Kinase A). Which of the following situations will result in the cellular response?

		The G protein releases GDP and binds to GTP
		The target protein (adenylyl cyclase) is inactive
		The regulatory subunits of PKA (Protein Kinase A) are bound to the catalytic subunits
		The appropriate G protein is bound to GDP

2 points

QUESTION 7

Which of the following is found in only some signal transduction pathways? [In other words, which is not found in all signal transduction pathways?]

		Receptor protein
		Extracellular signal molecule
		Intracellular signaling molecule
		Cellular response
		Effector protein

2 points

QUESTION 8

The enzyme that specifically catalyzes the conversion of ATP to cAMP is:

		Adenylyl phosphatase
		Adenylyl kinase
		Adenylyl dehydrogenase
		Adenylyl cyclase

2 points

QUESTION 9

If an animal cell suddenly lost the ability to produce GTP, what might happen to its signaling system?

		It would use ATP instead of GTP to activate and inactivate the G protein on the cytoplasmic side of the plasma membrane.
		It would not be able to activate and inactivate the G protein on the cytoplasmic side of the plasma membrane.
		It would employ a transduction pathway directly from an external messenger.
		It would be able to carry out reception and transduction but would not be able to respond to a signal.

2 points

QUESTION 10

A hormone signal is sent from the brain to other parts of the body via the bloodstream. Why do only certain cells respond to this signal?

		Hormones do not last long enough in the bloodstream to stimulate a cellular response
		Only cells that have a specific transcription factor gene will be able to respond to the signal
		Only cells in the immediate vicinity of the cell sending the signal will respond
		Only cells that have a receptor for the specific signal will be able to respond to it

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BCHM 210 Study Guide - Midterm Guide: Receptor Tyrosine Kinase, Irs1, Insulin Receptor

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