Chapter 15 - Cell Communication Part 2: RTKs Flashcards

1
Q

What are the main types of enzyme-coupled receptors?

A

Receptor Tyrosine Kinases (RTKs), Tyrosine-Kinase-associated receptors, Receptor Serine/Threonine Kinases.

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2
Q

Describe the key structural feature of RTKs.

A

Single transmembrane domain with intrinsic tyrosine kinase activity in the cytosolic domain.

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3
Q

How are receptor tyrosine kinases (RTKs) activated?

A

By ligand binding, dimerization, and trans-autophosphorylation.

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4
Q

What is the role of SH2 domains in RTK signaling?

A

They bind phosphorylated tyrosine residues, recruiting signaling proteins.

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5
Q

What types of domains bind to phosphorylated tyrosines on RTKs?

A

SH2 and PTB domains.

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6
Q

Explain the MAPK pathway steps after Ras activation.

A

Ras activates Raf, which phosphorylates MEK, leading to ERK activation and gene expression.

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7
Q

How does PI3K/Akt signaling contribute to cell survival?

A

By phosphorylating and activating Akt, which promotes survival and growth.

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8
Q

What is the function of PTEN in the PI3K pathway?

A

PTEN dephosphorylates PIP3, inhibiting the PI3K/Akt signaling pathway.

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9
Q

Describe the structure of G-protein coupled receptors (GPCRs).

A

Seven transmembrane domains that activate G proteins upon ligand binding.

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10
Q

How do GPCRs amplify signals?

A

By activating G proteins that generate second messengers like cAMP, IP₃, and DAG.

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11
Q

Name two common second messengers in GPCR signaling.

A

cAMP and IP₃.

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12
Q

What enzyme produces cAMP in response to GPCR activation?

A

Adenylyl cyclase.

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13
Q

Explain the role of IP₃ in GPCR signaling.

A

IP₃ binds to receptors on the ER, releasing Ca²⁺ into the cytosol.

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14
Q

How does DAG function in signal transduction?

A

It activates protein kinase C (PKC) to modulate cellular responses.

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15
Q

What is the JAK-STAT pathway primarily activated by?

A

Cytokine receptors associated with JAK kinases.

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16
Q

What happens when JAKs are activated?

A

They phosphorylate STAT proteins, which dimerize and translocate to the nucleus to initiate transcription.

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17
Q

How do receptor Serine/Threonine kinases signal?

A

By phosphorylating Smad proteins in response to TGF-β signaling.

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18
Q

What is the role of scaffold proteins in MAPK signaling?

A

They organize kinase complexes to prevent pathway cross-talk.

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19
Q

How does Ras function as a molecular switch?

A

It is active when bound to GTP and inactivated when hydrolyzing GTP to GDP.

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20
Q

What is the role of GEFs in Ras activation?

A

GEFs exchange GDP for GTP on Ras, activating it.

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21
Q

Why are Ras mutations common in cancers?

A

Mutations lock Ras in an active state, promoting uncontrolled cell growth.

22
Q

How does the PI3K/Akt pathway contribute to cancer?

A

Overactive PI3K or loss of PTEN leads to prolonged cell survival and growth.

23
Q

Describe EGFR’s role in oncogenesis.

A

EGFR mutations or overexpression lead to constant RTK signaling, promoting cancer.

24
Q

What is regulated proteolysis in signaling?

A

A mechanism where proteolysis releases and activates key transcription factors.

25
Q

Which pathways depend on regulated proteolysis?

A

Wnt/β-Catenin, TNF/NF-κB, and Hedgehog pathways.

26
Q

How is β-Catenin regulated in the Wnt pathway?

A

Wnt binding prevents β-Catenin degradation, allowing it to activate target genes.

27
Q

Describe the NF-κB pathway activation.

A

TNF binding leads to IκB degradation, releasing NF-κB to enter the nucleus.

28
Q

What role does Hedgehog signaling play in development?

A

It regulates gene expression crucial for tissue patterning.

29
Q

How does cyclopamine affect the Hedgehog pathway?

A

It inhibits the pathway, causing developmental defects.

30
Q

How are tyrosine phosphatases involved in feedback regulation?

A

They remove phosphates from tyrosines to turn off RTK signaling.

31
Q

Explain the role of ubiquitination in receptor downregulation.

A

It tags receptors for internalization and degradation in lysosomes.

32
Q

How does mTOR contribute to cell growth?

A

It promotes protein synthesis and cell growth in response to Akt signaling.

33
Q

Describe the structure of the insulin receptor.

A

It consists of two α and two β chains linked by disulfide bonds.

34
Q

How does the insulin receptor activate glucose uptake?

A

By activating the PI3K/Akt pathway, leading to GLUT4 translocation to the membrane.

35
Q

What is the function of Src kinases?

A

Non-receptor tyrosine kinases that mediate immune cell signaling.

36
Q

How are Src family kinases regulated?

A

By SH2 and SH3 domain interactions that control kinase activity.

37
Q

What impact does a PTEN mutation have on cellular signaling?

A

Loss of PTEN prolongs PI3K signaling, leading to excessive cell survival and growth.

38
Q

How do GPCRs affect cardiac function?

A

By regulating ion channels to control heart rate and contraction strength.

39
Q

What is cross-talk in cell signaling?

A

Interaction between different signaling pathways that can lead to interference.

40
Q

What is the role of Gq protein in GPCR signaling?

A

It activates phospholipase C, producing IP₃ and DAG.

41
Q

How does PI3K activation affect the plasma membrane?

A

It phosphorylates PIP2 to PIP3, creating docking sites for signaling proteins.

42
Q

Why are tyrosine phosphorylations rare but significant?

A

They are mitogenic and essential for cell proliferation control.

43
Q

What initiates the transcriptional response in the JAK-STAT pathway?

A

Phosphorylated STAT dimers translocate to the nucleus.

44
Q

How does EGFR overexpression contribute to cancer?

A

It leads to excessive cell proliferation due to constant signaling.

45
Q

Name a common signaling pathway activated by growth factors.

A

The PI3K/Akt pathway for survival and growth.

46
Q

How does mTORC1 influence cell metabolism?

A

It increases protein synthesis and inhibits degradation.

47
Q

What are Smad proteins?

A

Transcription factors activated by receptor Serine/Threonine kinases in TGF-β signaling.

48
Q

How does ubiquitin tagging affect RTKs?

A

It marks them for degradation, controlling signal intensity.

49
Q

Describe a common pathway disrupted in cancer cells.

A

The PI3K/Akt pathway, often due to PTEN mutations.

50
Q

What is the function of phosphatases like PTPs?

A

They deactivate signaling pathways by removing phosphate groups.