Cell Signaling: JAK-STAT and RTK Pathways

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Questions and Answers

What is the role of the JAK kinase in the erythropoietin receptor signaling pathway?

It directly binds to the Epo protein to initiate signaling.

It phosphorylates adjacent Epo receptors to enhance affinity.

It promotes autophosphorylation leading to activation of cellular responses. (correct)

It acts as a ligand to stabilize the dimerized receptors.

What happens to the erythropoietin receptor when erythropoietin is available?

It dimerizes with another receptor, activating the intracellular signaling. (correct)

It becomes a monomer and loses its binding ability.

It undergoes conformational changes leading to receptor endocytosis.

It phosphorylates itself in the absence of any signal.

Which domain of the erythropoietin receptor is involved in interacting with JAK kinases?

Cytosolic domain (correct)

Endoplasmic reticulum domain

Extracellular domain

Transmembrane alpha-helix domain

What specific type of residues do JAK kinases phosphorylate upon activation?

Tyrosine residues Signup and view all the answers

What initiates the cascade of intracellular events after the erythropoietin receptor is activated?

Phosphorylation of docking sites on the receptor's cytosolic domain Signup and view all the answers

What is required for the SH2 domain to bind with high affinity to its target sequence?

A phosphorylated tyrosine residue Signup and view all the answers

Which of the following protein-interaction domains is NOT dependent on reversible modifications of the target peptide?

PDZ domains Signup and view all the answers

Which of the following proteins is activated by the erythropoietin receptor to regulate erythrogenesis?

STAT5 transcription factor Signup and view all the answers

What role does the Bcl-XL protein play in erythroid progenitor cells?

Inhibits apoptosis to allow cell persistence Signup and view all the answers

Where is erythrogenesis primarily regulated during development?

In the bone marrow Signup and view all the answers

What characterizes scaffold proteins as compared to monomeric adaptor proteins?

Scaffold proteins contain multiple protein-protein interaction domains. Signup and view all the answers

Which statement accurately describes the binding characteristics of the SH2 and SH3 domains?

The SH2 domain requires reversible phosphorylation for binding, whereas SH3 domains bind to proline-rich sequences. Signup and view all the answers

What role does the GTP-bound state of G-proteins play in their function?

It activates the protein, allowing it to participate in signaling pathways. Signup and view all the answers

What does the intrinsic GTPase activity of G-proteins indicate?

It is active at all times but can be modulated by external factors. Signup and view all the answers

How is the binding between the SH3 domain and its target protein characterized?

The binding relies on the specific molecular complementarity between the SH3 domain and proline-rich residues. Signup and view all the answers

What is primarily responsible for the activation of receptor tyrosine kinases (RTKs)?

Ligand binding to the external domain Signup and view all the answers

Which process follows the dimerization of RTKs after ligand binding?

Autophosphorylation of tyrosine residues Signup and view all the answers

What is the role of Ras proteins in cell signaling?

They act as molecular switches in signaling pathways Signup and view all the answers

How does Ras protein activation influence downstream signaling?

By activating a cascade of cellular events Signup and view all the answers

What occurs upon the autophosphorylation of RTKs?

Docking sites for signaling molecules are created Signup and view all the answers

What is the primary role of RTKs once activated by ligand binding?

To phosphorylate additional intracellular proteins. Signup and view all the answers

Which of the following best describes the function of the MAPK pathway?

It regulates cell growth, proliferation, and differentiation. Signup and view all the answers

What mechanism contributes to the precise regulation of signal transduction pathways?

Feedback loops that fine-tune signaling. Signup and view all the answers

Which of the following pathways is primarily linked to calcium mobilization and cytoskeletal rearrangements?

PLCγ pathway Signup and view all the answers

How do signal transduction pathways typically amplify the original signal?

Through a series of protein-protein interactions that involve protein kinases. Signup and view all the answers

Study Notes

Module 6, Lecture 2: Cell Signaling - Phosphorylation

Objectives: Describe key steps in two signal transduction pathways: cytokine receptor/JAK-STAT and receptor tyrosine kinase (RTK)/Ras. Identify similarities and differences between these pathways and interpret experimental results defining pathway components.

Cytokine Receptors and JAK-STAT Pathway

Erythrocyte production: ~2 million red blood cells produced per second in adults.
Development: Develop in bone marrow, circulate for ~4 months, replaced by pluripotent stem cells differentiating into mature erythrocytes.
Erythropoietin (Epo): Cytokine signal regulating erythropoiesis. Produced in kidneys, released into circulation.
Epo Receptor (EpoR): Only erythrocyte progenitor cells carry this receptor.
JAK-STAT Pathway: Cytokine receptor (EpoR) is inactive as a monomer. Epo binding triggers receptor dimerization & activation of associated JAK kinases. JAK kinases phosphorylate each other (autophosphorylation) resulting in higher kinase activity targeting tyrosine residues on the receptor itself.
Cellular Responses: Inhibition of cell death, changes in gene expression, differentiation; these occur in target cells, such as erythrocyte progenitors.

Receptor Tyrosine Kinases (RTK)

Structure: Extracellular signal binding domain, transmembrane domain, and intrinsic kinase activity in the cytoplasmic domain.
Ligand binding: Epo binding triggers receptor dimerization and autophosphorylation of the receptor, increasing kinase activity.
Intracellular Signal Transduction: Longer pathways than cytokine systems. Activation of intracellular proteins (e.g., Ras) involving scaffold proteins, adapter proteins (GRB2) and downstream kinases (e.g., MAP kinase).
Ras activation: Ras-GDP interacts with GEF (e.g, SOS) activating Ras into Ras-GTP, further activating downstream pathways.
Downstream activation: Various protein phosphorylation cascades (e.g., Raf, MEK, MAP kinase) leading to changes in gene expression within the nucleus inducing cell division, differentiation, or apoptosis.

Turning off the pathways

De-phosphorylation: The reversal of phosphorylation by phosphatases (e.g., SHP-1) is key for shuttling off the system temporarily.
Receptor recycling/signal release: Receptors are internalized through endocytosis. This permanently disables downstream signalling, when concentrations of the ligand or signal drop.
SOCS proteins: Bind to phosphorylated docking sites, blocking access to substrates (e.g., STAT). This is a longer-term inactivation mechanism. Ubiquitination and degradation of JAK kinases and further proteins are also a part of the process.

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Description

Explore the essential mechanisms of cell signaling through the cytokine receptor/JAK-STAT and receptor tyrosine kinase (RTK)/Ras pathways. This quiz covers the role of erythropoietin in erythrocyte production and the key steps involved in each pathway. Learn to identify similarities and differences between these signal transduction pathways.