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Questions and Answers
What is the primary role of protein phosphorylation in cellular processes?
What is the primary role of protein phosphorylation in cellular processes?
Which of the following statements about structural domains is true?
Which of the following statements about structural domains is true?
What process contributes to the variability of structural domains in proteins?
What process contributes to the variability of structural domains in proteins?
Which of the following is an example of a catalytic domain?
Which of the following is an example of a catalytic domain?
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What distinguishes PTB and SH2 domains from each other?
What distinguishes PTB and SH2 domains from each other?
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How do cellular proteins interpret chemical modifications such as phosphorylation?
How do cellular proteins interpret chemical modifications such as phosphorylation?
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What happens to the tetrameric structure of PKA when four cAMP molecules bind to its regulatory subunits?
What happens to the tetrameric structure of PKA when four cAMP molecules bind to its regulatory subunits?
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Which of the following statements accurately reflects the nature of structural domains?
Which of the following statements accurately reflects the nature of structural domains?
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Which domain is associated with enzymatic activity specifically related to removing phosphate groups?
Which domain is associated with enzymatic activity specifically related to removing phosphate groups?
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What is the role of the protein interaction domains?
What is the role of the protein interaction domains?
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What initiates the intracellular signaling process?
What initiates the intracellular signaling process?
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Which mechanism is NOT involved in signal transduction cascades within a cell?
Which mechanism is NOT involved in signal transduction cascades within a cell?
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How do structural domains of signaling proteins contribute to signal propagation?
How do structural domains of signaling proteins contribute to signal propagation?
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What is the primary role of scaffold proteins in signaling pathways?
What is the primary role of scaffold proteins in signaling pathways?
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What is the significance of non-covalent interactions between signaling proteins?
What is the significance of non-covalent interactions between signaling proteins?
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Which of the following best describes protein-protein interactions in signaling cascades?
Which of the following best describes protein-protein interactions in signaling cascades?
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What happens to the ligand-receptor complex upon binding?
What happens to the ligand-receptor complex upon binding?
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Why is signal specificity important in intracellular signaling?
Why is signal specificity important in intracellular signaling?
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What is the main characteristic of proline-rich sequences that SH3 domains interact with?
What is the main characteristic of proline-rich sequences that SH3 domains interact with?
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Which of the following proteins is an example of a protein containing SH3 domains?
Which of the following proteins is an example of a protein containing SH3 domains?
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Which type of domain binds to phosphotyrosine residues?
Which type of domain binds to phosphotyrosine residues?
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What is a key function of PH domains in cellular processes?
What is a key function of PH domains in cellular processes?
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What is the general role of Src family kinases in cellular processes?
What is the general role of Src family kinases in cellular processes?
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Which protein is cited as an example of a PH-domain containing protein?
Which protein is cited as an example of a PH-domain containing protein?
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In which structural conformation do Src family kinases become active?
In which structural conformation do Src family kinases become active?
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Which domain is specifically associated with calcium binding?
Which domain is specifically associated with calcium binding?
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What is the primary function of a PDZ binding motif?
What is the primary function of a PDZ binding motif?
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Which of the following proteins is considered a PDZ-based scaffold protein?
Which of the following proteins is considered a PDZ-based scaffold protein?
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What characterizes MAGUK proteins?
What characterizes MAGUK proteins?
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Which of the following is a function of scaffold proteins?
Which of the following is a function of scaffold proteins?
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Which scaffold protein is involved in the Drosophila melanogaster phototransduction cascade?
Which scaffold protein is involved in the Drosophila melanogaster phototransduction cascade?
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Which domain is NOT found in MAGUK proteins?
Which domain is NOT found in MAGUK proteins?
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What does the abbreviation 'MAGUK' stand for?
What does the abbreviation 'MAGUK' stand for?
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Which protein is known as the Na H Exchanger regulatory factor?
Which protein is known as the Na H Exchanger regulatory factor?
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What is the primary role of AKAP in cellular signaling?
What is the primary role of AKAP in cellular signaling?
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Which of the following proteins directly interacts with phosphorylated receptors?
Which of the following proteins directly interacts with phosphorylated receptors?
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Which kinases are non-covalently associated with cytokine receptors to initiate signaling?
Which kinases are non-covalently associated with cytokine receptors to initiate signaling?
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How do STATs become activated after binding to the phosphorylated receptor?
How do STATs become activated after binding to the phosphorylated receptor?
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What distinguishes cytokine receptors from receptor tyrosine kinases (RTKs)?
What distinguishes cytokine receptors from receptor tyrosine kinases (RTKs)?
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What role does the COOH-terminal end of G-protein coupled receptors (GPCRs) serve?
What role does the COOH-terminal end of G-protein coupled receptors (GPCRs) serve?
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Which domain of STATs is crucial for their binding to phosphorylated receptors?
Which domain of STATs is crucial for their binding to phosphorylated receptors?
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Which of the following is NOT considered a signaling scaffold protein?
Which of the following is NOT considered a signaling scaffold protein?
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Study Notes
Bioc 325: Lecture 2
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Learning Objectives: Introduce signaling structural domains, their roles in signal propagation, and the importance of scaffold proteins.
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Introduction: Intracellular signaling translates messages for cellular responses. The initial step involves ligand-receptor interaction causing conformational changes. Common mechanisms include protein-protein interactions and phosphorylation.
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Protein-Protein Interactions: Signal propagation through the intracellular space requires protein interaction. It maintains signal specificity and occurs in a tightly controlled mode, not randomly. Protein interactions are restricted to authorized partners. Protein modules (interaction motifs) are key.
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Protein Phosphorylation: A popular mechanism for transmitting information along cascades. It occurs when a protein kinase interacts with tyrosine, threonine, or serine residues on a protein which serves as a signal for activating or deactivating downstream events.
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Part 1: Structural Domains:
- Domains are regions of similar architecture within proteins, serving as functional components.
- Domains are modular, repeating within a single polypeptide or recurring in various protein structures.
- Some domains have different structures but the same function (e.g., PTB and SH2 bind p-Tyr).
- Some domains have the same structure but different functions (e.g., PTB and PH).
- Most proteins contain at least two domains and signaling molecules often have more.
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Structural Domains and Their Roles:
- Domains play key roles as functional components.
- Individual domains may not guarantee a specific function but may contribute to it.
- Exon mutations and shuffling affect a domain's function.
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A: Catalytic Domains: Possess enzymatic activity. Examples include protein kinase domains (like PKA, PKC, RTKs) and phosphatase domains (like PTEN).
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B: Protein Interaction Domains: Lack enzymatic activity. These provide interaction sites for other proteins. Examples include SH2 and SH3 domains.
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Classification of Structural Domains: Domains are classified by their function in cellular signaling:
- Domains that bind to oligopeptide motifs (SH2, SH3, PTB)
- Phosphoinositide-binding domains (PH)
- Ca2+-binding domains (EF-hand and C2)
- Zinc finger domains (C2H2)
- Protein kinase domains
- PDZ domains
SH2 Domains
- Nomenclature: SH2 = Src homology region 2.
- Function: Protein interaction domains that bind to short motifs with phosphotyrosine.
- Examples: Receptor tyrosine kinases (RTKs), non-RTKs, phospholipase Cy (PLCγ), regulatory subunits of phosphoinositide 3-kinase (PI3K), and some protein tyrosine phosphatases (PTPs).
SH3 Domains
- Nomenclature: SH3 = Src homology region 3.
- Function: Protein interaction domains that bind to proline-rich sequences.
- Proline-rich Sequences: Typically consist of 8-10 proline residues, including at least two prolines in a PxxP motif.
- Hydrophobic Binding: SH3 domains have a hydrophobic binding surface.
- Examples: Adaptor proteins such as Grb2 and Nck.
PTB Domains
- Nomenclature: PTB = PhosphoTyrosine Binding.
- Function: Bind phosphotyrosine residues (N-P-X-pY), but recognize sequences that are quite distinct from SH2 domains.
- Phospholipid Binding: Also can bind acidic phospholipid head groups like those in phosphoinositides.
- Importance: Can translocate to membrane surfaces to encounter ligands.
- Example: PTB domain of insulin receptor substrate-1 (IRS-1).
PH Domains
- Nomenclature: PH = Pleckstrin Homology.
- Physiological Ligands: Phosphoinositides and βy-subunits of G proteins.
- Role: Involved in protein-protein interactions.
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Role: Example: Interaction of GRK2 (G-protein receptor kinase 2) with activated β-adrenergic receptors.
- Examples: pleckstrin, GRK2, PLC, Akt
Ca2+ binding motifs
- EF-hand motifs: Helix-loop-helix motifs that recognize and bind to calcium. Typically occur as adjacent pairs for enhanced function.
- C2 domains: Second conserved regulatory domain of PKCB, recognizing and binding to calcium.
Zinc Finger Domains
- C2H2 Domains: The largest zinc finger family, where zinc is coordinated by two cysteine and two histidine residues forming a stable complex.
Protein Kinase Domains
- Function: Catalytic domains with intrinsic activity. Examples are the catalytic subunits of PKA, PKC, RTKs
PDZ Domains
- Function: Bind to C-terminal residues of ion channels and receptors. Some can also bind to phosphoinositides. They help to anchor transmembrane proteins to the cytoskeleton and hold signaling complexes together.
Part 2: PDZ and Non-PDZ-based Scaffold Proteins
- Definition: Proteins that associate with two or more other proteins to enhance the efficiency and/or specificity of a cellular pathway.
PDZ-based Scaffold Proteins
- Specific examples include InaD, PSD-95, NHERF, and MAGUK proteins.
Non-PDZ-based Scaffold Proteins
- Specific examples include AKAP, JAK-STAT, and β-arrestin.
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Description
Test your knowledge on the roles of protein phosphorylation and structural domains in cellular processes. Explore how modifications like phosphorylation influence signaling pathways and the interactions among proteins. Challenge yourself with questions about catalytic domains and the nature of signal transduction.