Receptor Tyrosine Kinases Quiz

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary function of receptor tyrosine kinases (RTKs)?

To regulate cell differentiation and proliferation (correct)

To transport ions across the plasma membrane

To act solely as a structural support in membranes

To trigger apoptosis in response to signaling

What structure is formed when ligand binds to receptor tyrosine kinases?

A trimeric receptor complex

An inactive conformation

A single monomer

A receptor dimer (correct)

Which of the following represents a common ligand for RTKs?

Insulin (correct)

Calcium ions

Cyclic AMP

Nitric oxide

What is the role of the intrinsic tyrosine kinase activity of RTKs?

To phosphorylate tyrosine residues on the receptor and downstream proteins Signup and view all the answers

How do RTKs typically activate intracellular signaling pathways?

By recruiting a complex of intracellular signaling proteins Signup and view all the answers

What is one consequence of the phosphorylation of the activation lip in RTKs?

Autophosphorylation leading to receptor activation Signup and view all the answers

Which of the following signaling proteins is most commonly activated by RTKs?

Monomeric GTPase Ras Signup and view all the answers

Which mechanism do cells use to regulate responses to chemical signals?

Desensitization of receptors through phosphorylation Signup and view all the answers

What is the role of Ras in RTK signaling?

It cycles between GDP-bound and GTP-bound forms. Signup and view all the answers

How do RTKs activate the PI3-Kinase signaling pathway?

By recruiting PI3-kinase to the membrane. Signup and view all the answers

Which protein kinase is directly phosphorylated by Raf in the MAP kinase signaling pathway?

MEK. Signup and view all the answers

What type of signaling proteins do phosphorylated lipids in the PI3-kinase pathway create?

Lipid docking sites. Signup and view all the answers

Which isoform of phospholipase C is activated by RTKs?

PLCγ. Signup and view all the answers

In what cellular process does phosphorylated MAP kinase participate after translocating to the nucleus?

Gene expression regulation. Signup and view all the answers

What is the main function of Akt in cell signaling?

To promote cell survival. Signup and view all the answers

What does the SH2 domain in GRB2 bind to?

Specific phosphotyrosines in activated RTKs. Signup and view all the answers

What initiates receptor dimerization in the signaling pathway of cytokines?

Ligand binding Signup and view all the answers

Which molecules are brought into close proximity due to receptor dimerization?

JAKs Signup and view all the answers

What is the consequence of the phosphorylation of STAT proteins?

They translocate to the nucleus. Signup and view all the answers

What role does JAK play in the signaling pathway after receptor dimerization?

It phosphorylates transcription factors. Signup and view all the answers

Which of the following best describes the function of STAT proteins in the signaling pathway?

They bind to phosphorylated docking sites on the receptor. Signup and view all the answers

What is the result of activated STATs moving into the nucleus?

They regulate the transcription of target genes. Signup and view all the answers

Which pathway is activated by receptor tyrosine kinases (RTKs)?

Ras monomeric GTPase signaling Signup and view all the answers

What is an example of crosstalk in signaling pathways?

Kinases phosphorylating proteins in other pathways Signup and view all the answers

What is the primary role of Akt in the PI-3-kinase signaling pathway?

To inhibit apoptosis by inactivating Bad Signup and view all the answers

How is Protein Kinase B (PKB) activated in the signaling pathway?

By phosphorylation from PDK1 and PDK2 kinases after membrane recruitment Signup and view all the answers

What is the effect of Akt on glycogen synthase kinase during insulin receptor signaling?

Akt phosphorylates and inactivates glycogen synthase kinase, stimulating glycogen synthesis Signup and view all the answers

What ultimately terminates the PI-3-kinase/Akt signaling pathway?

Cleavage of 3-phosphates from phosphoinositides by PTEN Signup and view all the answers

What effect does Akt have on cell growth?

It increases cell growth by activating Tor Signup and view all the answers

What is the role of Sos in the activation of Ras?

It promotes GTP exchange for GDP on Ras. Signup and view all the answers

How does Ras activate the MAP kinase pathway?

Through a phosphorylation cascade involving Raf and MEK. Signup and view all the answers

What occurs when receptors undergo endocytosis at high ligand concentrations?

They are degraded in lysosomes, reducing cell sensitivity. Signup and view all the answers

Which proteins help regulate GTP binding and hydrolysis for Ras?

Guanine nucleotide-exchange factors and GTPase-activating proteins. Signup and view all the answers

What can dominant Ras mutations lead to regarding cell signaling?

Prolonged activation of MAP kinase signaling. Signup and view all the answers

Which of the following correctly describes MAP kinases?

They propagate signals by phosphorylating transcription factors. Signup and view all the answers

What is a significant feature of receptor tyrosine kinases (RTKs)?

They can dimerize when binding to ligands. Signup and view all the answers

What is the final outcome of the RTK-Ras/MAP kinase signaling pathway?

Phosphorylation and activation of genes that regulate cell division. Signup and view all the answers

What is the primary role of Tor in cellular processes?

Stimulates protein synthesis and inhibits degradation Signup and view all the answers

How do mutant proteins help in cellular signaling research?

By providing a tool to determine binding locations of signaling molecules Signup and view all the answers

What happens during the activation of receptor tyrosine kinases (RTKs)?

They recruit intracellular signaling proteins Signup and view all the answers

Which of the following correctly describes the role of Janus Kinases (JAKs) in the signaling pathway of cytokines?

They cross-phosphorylate and activate one another upon cytokine binding. Signup and view all the answers

What is the function of signal transducers and activators of transcription (STATs)?

They migrate to the nucleus after activation to regulate target gene transcription. Signup and view all the answers

Which statement about the action of cytokines is true?

Binding of cytokines activates a distinct signaling pathway through receptor interaction. Signup and view all the answers

What is an example of a cytokine's effect on a specific cell type?

Stimulating breast cells to produce milk upon prolactin hormone activation. Signup and view all the answers

What effect does a constitutively active form of Ras have on signal transmission?

It transmits signals regardless of extracellular signals present. Signup and view all the answers

Study Notes

Learning Outcomes

Session 1 learning outcome: Define kinases and phosphatases and their roles in signal transduction.
Session 2 learning outcome: Explain the different mechanisms by which cells regulate and/or terminate responses to chemical signals.

Enzyme-Coupled Receptors

Enzyme-coupled receptors are transmembrane proteins.
These proteins display their ligand-binding domain on the outer surface of the plasma membrane.
The cytoplasmic domain of the receptor acts as an enzyme or forms a complex with another protein that serves as an enzyme.

Receptor Tyrosine Kinases (RTKs)

RTKs are the largest class of enzyme-coupled receptors.
They consist of receptors with a cytoplasmic domain that functions as a tyrosine protein kinase.
These kinases phosphorylate specific tyrosine residues on selected intracellular proteins.

Receptor Tyrosine Kinases (RTKs) - Regulation

RTKs regulate cell proliferation and differentiation.
Ligands for RTKs are soluble or membrane-bound peptide/protein hormones.
Examples of these hormones include NGF, PDGF, FGF, EGF, and insulin.
Ligand binding causes receptor dimerization; in some cases (e.g., insulin RTK), binding occurs to pre-existing dimers.

Signaling Proteins Acting Via Receptor Tyrosine Kinases

Ligands include and examples of the respective Receptor proteins: EGF and EGF receptor, Insulin and Insulin receptor, IGF-1, IGF-2, and IGF receptor-1, NGF and TrkA, PDGF, PDGF receptors (a and β), M-CSF and M-CSF receptor, FGF, FGF receptor, VEGF and VEGF receptor, Ephrins and Eph receptors.
Corresponding responses associated with the signaling are also listed.

Enzyme-Coupled Receptors - Further Details

Activated RTKs recruit a complex of intracellular signaling proteins.
Most RTKs activate the monomeric GTPase Ras.
RTKs activate PI 3-kinase to produce lipid docking sites in the plasma membrane.
Some receptors directly activate a fast track to the nucleus.
Protein kinase networks integrate information to control complex cell behaviors.

RTK Signaling Pathways

Nearly all RTKs signal via Ras/MAP kinase pathways, but other pathways exist.
For example, insulin receptor uses Ras/MAP kinase to regulate gene expression and PI-3 kinase to regulate enzyme activity (e.g., glycogen synthase).

Ras Activation

Ras is a small protein bound to a lipid tail in the cytoplasmic face of the plasma membrane.
Ras-activating protein causes GDP to exchange to GTP activating Ras making it stimulate the next steps in the signaling pathway.
Ras recruits and stimulates the Ras activating protein.

MAP Kinase Pathway

MAP kinase is a protein kinase that performs a crucial step in relaying signals from cell-surface receptors to the nucleus, being the final step in a 3-kinase sequence (mitogen-activated protein kinase)
MAP kinase phosphorylates and regulates downstream target proteins, which include transcription regulators.
Change in gene expression and protein activity result in complex changes in cell behavior like proliferation and differentiation.

RTK Activity and Ras Activation

EGF binding to receptor leads to dimerization and autophosphorylation on cytosolic tyrosines.
Binding hormone causes receptor dimerization, kinase activation, and phosphorylation of cytosolic receptor tyrosine residues.

Adaptor Protein GRB2

The adaptor protein GRB2 binds to receptor phosphotyrosine residues via its SH2 domain.
Binding of GRB2 and Sos protein couples the receptor to inactive Ras.
GRB2 contains SH3 domains, which allow the GEF protein (Sos) to bind the membrane complex and recruit Ras.

Ras-GTP Complex

The activated Ras-GTP complex dissociates from Sos but remains tethered to the inner leaflet of the cytoplasmic membrane through a lipid anchor sequence.
Activated Ras activates the MAP kinase portion of the signaling pathway.

Ras and Gα Subunits

Activation of Ras and Gα subunits is triggered by hormone binding to a cell-surface receptor.
Ras is a monomeric small GTPase switch protein.

Ras-GTP Hydrolysis

Ras typically relies on GEFs for binding GTP and on GAPs for stimulation of GTP hydrolysis.

Other RTK Functions

Once activated, Ras propagates signaling through a kinase cascade, resulting in the activation of MAP kinase family members.
MAP kinase phosphorylates TFs regulating genes involved in the cell cycle and differentiation.
RTK–Ras/MAP kinase signaling controls cell division, differentiation, and metabolism.

Receptor Internalization

At high ligand concentrations, some cell surface receptors are internalized via endocytosis.
Receptor internalization reduces the number of receptors on the cell surface and makes cells less sensitive to the ligand.

Mutant RTKs and Cancers

Mutant RTKs or Ras/MAP kinase signaling proteins are commonly associated with cancers.
Dominant Ras mutations that prevent GAP binding and lock Ras in the "on" state promote cancer.

MAP Kinase Cascade

Ras activates MAP kinase via a phosphorylation cascade from Ras, Raf kinase, MEK kinase, and MAP kinase.
Active MAP kinase translocates to the nucleus and activates many transcription factors.

Final Steps RTK-Ras MAP Kinase Signaling

MAP kinase phosphorylates and activates p90RSK kinase in the cytoplasm.
Both kinases enter the nucleus, phosphorylate transcription factors, and activate expression of genes that propel cells through the cell cycle.

Summary of RTK Signaling

RTKs bind peptide hormones, behaving as dimers or dimerizing upon ligand binding.
Ligand binding activates the receptor kinase, causing autophosphorylation of tyrosine residues.
Ras, an intracellular GTPase, acts downstream from most RTKs and cycles between active (GTP-bound) and inactive (GDP-bound) forms.
RTKs are coupled to Ras via GRB2 and Sos.
Phosphorylated MAP kinase translocates into the nucleus and activates or inactivates transcription factors.

Summary of SH2 Domain in GRB2

The SH2 domain in GRB2 is an adaptor protein that binds to specific phosphotyrosines in activated RTKs.
Raf is recruited to the membrane by binding to Ras–GTP and activated, phosphorylating MEK, a dual specificity kinase that phosphorylates MAP kinase.
Phosphorylated MAP kinase dimerizes and translocates to the nucleus, regulating gene expression.

PI-3-kinase-Akt Pathway

RTKs can activate the PI-3-Akt signaling pathway.
Extracellular survival signals (e.g., IGF) activate an RTK, which recruits and activates PI 3-kinase.
This pathway promotes cell growth and survival.

PI3-Kinase Signaling

PI3-kinase is an enzyme that phosphorylates inositol phospholipids in the plasma membrane.
Phosphorylated lipids become docking sites for intracellular signaling proteins which move from cytosol to the membrane.

Activated Akt and Cell Survival

Akt, a serine/threonine kinase, is one of the signaling proteins in the PI-3 kinase pathway.
Akt promotes cell survival by inactivating Bad (a cytosolic protein) and thus inhibiting apoptosis.

PI3-Kinase-Akt and Tor

Activated Akt activates Tor, a serine/threonine kinase.
Tor stimulates protein synthesis and inhibits protein degradation, which promotes cell growth.

Inhibition of Receptor Tyrosine Kinases

Excess mutant receptors can inhibit signaling through normal receptor tyrosine kinases.
Mutant receptors lack kinase activity, preventing cross-phosphorylation of signaling proteins.

Mutant Proteins and Signaling

Mutant proteins can help identify precise binding sites on intracellular signaling molecules.

Jamming the Pathway

Recombinant DNA technology enables the creation of constitutively active forms of proteins like Ras.
Constitutively active proteins mimic the effects of extracellular signals even without their presence.

Ras Mutations and Cancer

Activating mutations in Ras (H-Ras, K-Ras, and N-Ras) are found in around 30% of human cancers.
Mutations in Ras regulators like NF1 are also associated with certain cancers.

Enzyme-Linked Receptors and Nucleus

Some enzyme-linked receptors activate a fast track to the nucleus.
Cytokines bind to their receptors, activating JAK kinases that phosphorylate STATs, which enter the nucleus to control gene expression.

Cytokine Signaling Pathway

The binding of cytokines causes a structural change to the receptor, leading to its dimerization.
JAKs are brought into proximity and cross-phosphorylate each other, thus becoming activated.
Activated JAKs phosphorylate tyrosine residues on the cytoplasmic tail of the receptor creating docking sites for STAT proteins.
STAT proteins bind to the phosphorylated docking sites and are also activated by the JAKs.
Activated STAT proteins dimerize and translocate to the nucleus.
STAT dimers then bind to specific DNA sequences, thus regulating the transcription of target genes.

Summary of Pathways

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on receptor tyrosine kinases (RTKs) and their signaling pathways. This quiz covers the functions, structures, and mechanisms behind RTK activation and their role in cellular signaling. Challenge yourself with questions about ligands, phosphorylation, and downstream effects of RTK signaling.