Enter a player name to begin or load your saved progress.
Protein Kinase C (PKC) is primarily characterized by its enzymatic function in dephosphorylating proteins, thereby reversing the activity of kinase enzymes.
Answer: False
Explanation: The source material clarifies that Protein Kinase C (PKC) is a family of enzymes that function by phosphorylating proteins, not by dephosphorylating them.
The official Enzyme Commission (EC) number assigned to Protein Kinase C is 2.7.11.13.
Answer: True
Explanation: The Enzyme Commission (EC) number 2.7.11.13 is indeed the official classification for Protein Kinase C.
In humans, there are precisely twelve known isozymes belonging to the Protein Kinase C family.
Answer: False
Explanation: Contrary to the statement, the source material indicates that there are fifteen known isozymes within the Protein Kinase C family in humans.
Professor Yasutomi Nishizuka is widely credited with the seminal discovery of Protein Kinase C.
Answer: True
Explanation: Yasutomi Nishizuka's pioneering research established the existence and fundamental role of Protein Kinase C.
Which of the following statements accurately describes the primary enzymatic function of Protein Kinase C (PKC)?
Answer: Phosphorylating hydroxyl groups on serine and threonine residues of proteins.
Explanation: The defining enzymatic activity of PKC is the transfer of a phosphate group from ATP to serine or threonine residues on substrate proteins.
What is the CAS registry number associated with Protein Kinase C as cited in the source material?
Answer: 141436-78-4
Explanation: The CAS registry number provided for Protein Kinase C is 141436-78-4.
The C1 domain, situated within the regulatory region of Protein Kinase C, is primarily responsible for binding diacylglycerol (DAG) and phorbol esters, not for sensing calcium ion concentrations.
Answer: True
Explanation: The C1 domain's primary function is to bind DAG and phorbol esters, while the C2 domain is responsible for sensing calcium ions.
The pseudosubstrate region of Protein Kinase C functions by mimicking a substrate protein, thereby maintaining the enzyme in an inactive state until specific activation signals induce its displacement.
Answer: True
Explanation: The pseudosubstrate region acts as an intramolecular inhibitor, blocking the active site until released upon appropriate cellular signaling.
The catalytic domain of Protein Kinase C exhibits significant sequence similarity to the catalytic domains of other serine/threonine-specific protein kinases.
Answer: False
Explanation: The catalytic domain of PKC is highly conserved and shows significant similarity to other serine/threonine kinases, not minimal similarity.
All Protein Kinase C enzymes are structurally characterized by the presence of a regulatory domain and a catalytic domain, interconnected by a flexible hinge region.
Answer: True
Explanation: This describes the fundamental domain organization common to all PKC isoforms.
The catalytic region of Protein Kinase C (PKC) shares approximately 40% amino acid sequence similarity with the catalytic region of Protein Kinase B (PKB), also known as Akt.
Answer: True
Explanation: Comparative sequence analysis reveals a significant degree of homology between the catalytic domains of PKC and PKB/Akt.
The C2 domain within the regulatory region of Protein Kinase C functions as a sensor for calcium ions (Ca2+), not as a binding site for diacylglycerol (DAG).
Answer: True
Explanation: The C2 domain's primary role is calcium binding, which is crucial for the membrane recruitment and activation of conventional PKC isoforms.
The crystal structures of the catalytic regions have been elucidated for specific Protein Kinase C (PKC) isoforms, namely PKC theta and PKC iota.
Answer: True
Explanation: Structural biology studies have determined the atomic resolution structures for the catalytic domains of PKC theta and PKC iota.
What are the two principal domains that constitute all Protein Kinase C enzymes?
Answer: Regulatory domain and catalytic domain
Explanation: All PKC isoforms are composed of a regulatory domain that mediates interactions with activators and a catalytic domain responsible for kinase activity.
The C1 domain, located within the regulatory region of Protein Kinase C, primarily functions to:
Answer: Bind diacylglycerol (DAG) or phorbol esters.
Explanation: The C1 domain is the primary site for binding DAG and related molecules, which is essential for the activation of conventional and novel PKC isoforms.
What is the specific role of the C2 domain within the Protein Kinase C enzyme?
Answer: It senses calcium ions (Ca2+).
Explanation: The C2 domain is responsible for binding calcium ions, a critical step in the membrane localization and activation of conventional PKC isoforms.
The pseudosubstrate region of Protein Kinase C is functionally significant because it:
Answer: Binds to the catalytic domain's active site, keeping the enzyme inactive.
Explanation: The pseudosubstrate region acts as an endogenous inhibitor by occupying the active site, preventing substrate phosphorylation until activation signals cause its release.
The catalytic region of Protein Kinase C (PKC) is characterized as highly conserved and exhibiting significant sequence similarity to the catalytic regions of which other enzyme class?
Answer: Serine/threonine-specific protein kinases
Explanation: The catalytic domain of PKC belongs to the conserved kinase fold shared by most serine/threonine protein kinases.
The crystal structures of the catalytic regions have been elucidated for which specific pair of Protein Kinase C (PKC) isoforms?
Answer: PKC theta and PKC iota
Explanation: Structural determination efforts have successfully resolved the crystal structures of the catalytic domains for PKC theta and PKC iota.
The consensus phosphorylation sequence motif for Protein Kinase C (PKC) enzymes bears similarity to that of Protein Kinase A (PKA) due to the presence of what specific feature?
Answer: Basic amino acids near the target serine/threonine residue.
Explanation: Both PKC and PKA recognize substrates with basic residues (like arginine or lysine) preceding the phosphorylated serine or threonine, contributing to sequence motif similarity.
Conventional Protein Kinase C (cPKC) isoforms necessitate the presence of diacylglycerol (DAG) for activation, yet are independent of calcium ions (Ca2+).
Answer: False
Explanation: Conventional PKC isoforms require both diacylglycerol (DAG) and calcium ions (Ca2+) for activation, along with phospholipids.
Atypical Protein Kinase C (aPKC) isoforms, exemplified by PKC zeta and iota, are activated by both diacylglycerol (DAG) and calcium ions (Ca2+).
Answer: False
Explanation: Atypical PKC isoforms are distinct in that they are activated independently of both diacylglycerol (DAG) and calcium ions (Ca2+).
The C1 domain in atypical Protein Kinase C (aPKC) isoforms is not functional for binding diacylglycerol (DAG).
Answer: True
Explanation: While present, the C1 domain in atypical PKCs lacks the necessary structural features to bind DAG or phorbol esters.
Phosphorylation of the activation loop and turn motif is essential for the activity of atypical Protein Kinase C (aPKC) isoforms, but not the hydrophobic motif.
Answer: True
Explanation: Atypical PKC isoforms are phosphorylated on the activation loop and turn motif, unlike conventional and novel isoforms which also require hydrophobic motif phosphorylation.
3-phosphoinositide-dependent protein kinase-1 (PDPK1) is primarily responsible for phosphorylating the activation loop, not the hydrophobic motif, in conventional Protein Kinase C (PKC) isoforms.
Answer: True
Explanation: PDPK1 initiates the phosphorylation cascade by phosphorylating the activation loop, which is a prerequisite for subsequent phosphorylations, including the hydrophobic motif by other kinases.
Conventional and novel Protein Kinase C (PKC) isoforms undergo phosphorylation on the activation loop, the turn motif, and the hydrophobic motif.
Answer: True
Explanation: These three phosphorylation sites are critical for the full activation and proper conformation of conventional and novel PKC isoforms.
Which intracellular signaling molecules are generally requisite for the activation of conventional (c)PKC isoforms?
Answer: Diacylglycerol (DAG) and calcium ions (Ca2+)
Explanation: Conventional PKC isoforms require both an increase in intracellular calcium and the presence of diacylglycerol for activation.
Novel Protein Kinase C (nPKC) isoforms (e.g., delta, epsilon, eta, theta) diverge from conventional isoforms primarily regarding their requirement for which specific second messenger?
Answer: They require DAG but not Ca2+.
Explanation: Novel PKC isoforms are activated by DAG but are independent of calcium ions, distinguishing them from conventional isoforms.
What characteristic uniquely defines the activation mechanism of atypical Protein Kinase C (aPKC) isoforms (e.g., zeta and iota)?
Answer: They require neither DAG nor Ca2+ for activation.
Explanation: Atypical PKC isoforms are activated through mechanisms independent of the second messengers DAG and Ca2+, relying instead on other regulatory inputs.
What is the principal role of 3-phosphoinositide-dependent protein kinase-1 (PDPK1) in the activation cascade of Protein Kinase C (PKC)?
Answer: It initiates PKC phosphorylation by phosphorylating the activation loop.
Explanation: PDPK1 is a crucial upstream kinase that phosphorylates the activation loop of PKC, a necessary step for subsequent full activation.
Which of the following is NOT recognized as a major subfamily of Protein Kinase C?
Answer: Intermediate (i)PKC
Explanation: The established subfamilies of PKC are conventional, novel, and atypical. An 'intermediate' subfamily is not recognized.
Which of the following Protein Kinase C (PKC) isoforms necessitates diacylglycerol (DAG) for activation but is independent of calcium ions (Ca2+)?
Answer: Novel (n)PKC isoforms like delta and epsilon
Explanation: Novel PKC isoforms require DAG for activation but do not require Ca2+, distinguishing them from conventional isoforms.
The Protein Kinase C (PKC) family is considered ancient in evolutionary terms, predating the divergence of vertebrates.
Answer: True
Explanation: Evidence suggests the PKC family originated much earlier in evolution, existing before the split that led to jawed vertebrates.
The Protein Kinase C (PKC) family is considered ancient, with evolutionary evidence indicating its presence prior to which significant phylogenetic divergence?
Answer: The divergence of jawed vertebrates
Explanation: The PKC family predates the evolutionary split leading to jawed vertebrates, indicating its ancient origins.
The source material indicates that the Protein Kinase C (PKC) family expanded from five ancestral members in jawed vertebrates via which evolutionary mechanism?
Answer: Genome duplication events
Explanation: Whole genome duplication events are considered the primary mechanism driving the expansion and diversification of the PKC gene family in vertebrates.
The functional effects of Protein Kinase C (PKC) exhibit cell-type specificity, primarily due to variations in the expression of its substrate proteins across different cell types.
Answer: True
Explanation: The diverse roles of PKC are realized through its interaction with specific substrates, which vary in abundance and type depending on the cell's identity and function.
Which of the following represents a known substrate protein that can be phosphorylated by Protein Kinase C (PKC) enzymes?
Answer: MARCKS protein
Explanation: MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) is a well-established substrate for PKC, involved in actin cytoskeleton regulation.
By what mechanism does the cell-type specificity of Protein Kinase C (PKC) effects manifest?
Answer: Based on the specific substrate proteins available for phosphorylation in each cell type.
Explanation: While different isoforms are expressed in different tissues, the ultimate specificity of PKC's cellular effects is largely determined by the unique set of substrate proteins present in each cell type.
Microgravity has been demonstrated to disrupt the translocation of Protein Kinase C (PKC) to the cell membrane, a phenomenon linked to potential negative impacts on astronaut health.
Answer: True
Explanation: Studies indicate that microgravity interferes with PKC translocation, which is associated with the immunodeficiency observed in astronauts.
Protein Kinase C (PKC) is implicated in the processes of learning and memory, contributing to its designation as a 'memory kinase'.
Answer: True
Explanation: PKC's role in synaptic plasticity and memory formation underlies its classification as a 'memory kinase'.
The observation of loss-of-function mutations and reduced protein levels of Protein Kinase C (PKC) in various cancers suggests that PKC generally functions as a tumor suppressor.
Answer: True
Explanation: The pattern of mutations and reduced expression in cancer indicates that PKC often acts to inhibit cell proliferation and tumor development.
Protein Kinase C (PKC) enzymes are implicated in vascular diseases, notably by mediating vascular permeability.
Answer: True
Explanation: PKC's role in regulating endothelial cell junctions contributes to vascular permeability, a factor in diabetic complications and smoke-induced injury.
Activation of Protein Kinase C (PKC) in proximal convoluted tubule cells stimulates proton secretion and enhances sodium reabsorption by upregulating the activity of the NHE3 transporter and the Na-K ATPase.
Answer: True
Explanation: PKC signaling plays a key role in regulating ion transport in renal tubules, contributing to homeostasis.
Protein Kinase C (PKC) enzymes are implicated in the pathogenesis of vascular diseases by mediating increased vascular permeability, a process relevant to complications in diabetes mellitus and damage induced by cigarette smoke.
Answer: True
Explanation: PKC's influence on endothelial barrier function contributes to vascular dysfunction observed in conditions like diabetes and smoking-related pathologies.
Protein Kinase C (PKC) plays a significant role in regulating smooth muscle contraction across diverse tissues, such as the gastrointestinal tract and the uterus.
Answer: True
Explanation: PKC signaling is integral to the physiological control of smooth muscle tone in various organs.
In what manner does the activation of Protein Kinase C (PKC) contribute to the neurobiological processes of learning and memory?
Answer: By phosphorylating proteins involved in synaptic plasticity and memory formation.
Explanation: PKC modulates synaptic efficacy and plasticity through the phosphorylation of key proteins, which is fundamental for learning and memory consolidation.
What is the implication of observed loss-of-function mutations and reduced protein levels of Protein Kinase C (PKC) in the context of cancer?
Answer: PKC acts as a tumor suppressor, inhibiting tumor growth.
Explanation: The loss of PKC function in cancer suggests its normal role is to restrain cell proliferation and tumor progression.
Protein Kinase C (PKC) enzymes are implicated in vascular diseases through their mediation of which critical physiological process?
Answer: Vascular permeability
Explanation: PKC activation can increase the permeability of blood vessels, contributing to pathological conditions.
According to the provided source material, how does microgravity impact Protein Kinase C (PKC) translocation, and what is a known consequence for astronaut health?
Answer: Disrupts translocation, linked to immunodeficiency.
Explanation: Microgravity interferes with PKC's proper localization within cells, which is associated with compromised immune responses in astronauts.
In what manner does Protein Kinase C (PKC) contribute to renal function within proximal convoluted tubule cells?
Answer: By enhancing proton secretion via NHE3 and sodium reabsorption.
Explanation: PKC activation in proximal tubule cells promotes the reabsorption of sodium and secretion of protons by modulating key transporters like NHE3 and Na-K ATPase.
What is the potential role of Protein Kinase C (PKC) activation, particularly when induced by tumor promoters such as phorbol esters, in the context of oncogenesis?
Answer: Leading to increased expression of oncogenes.
Explanation: Activation of PKC by tumor promoters can lead to the phosphorylation of transcription factors that drive the expression of oncogenes, thereby promoting cancer development.
Ruboxistaurin is a Protein Kinase C inhibitor investigated for its potential therapeutic use in treating peripheral diabetic nephropathy.
Answer: True
Explanation: Ruboxistaurin, a PKC inhibitor, has been studied for its efficacy in managing peripheral diabetic nephropathy.
Ingenol mebutate, a compound derived from the plant *Euphorbia peplus*, has received regulatory approval for the treatment of actinic keratosis.
Answer: True
Explanation: Ingenol mebutate is an approved therapeutic agent for actinic keratosis, functioning as a PKC activator.
12-O-Tetradecanoylphorbol-13-acetate (PMA) mimics diacylglycerol (DAG), not calcium ions, and is known to activate conventional and novel PKC isoforms, not atypical ones.
Answer: True
Explanation: PMA acts as a DAG analogue, activating classical and novel PKC isoforms, and does not mimic calcium ions or activate atypical isoforms.
Bryostatin 1 is described as a naturally occurring compound that acts as a selective activator, not an inhibitor, of Protein Kinase C (PKC).
Answer: False
Explanation: The source material lists Bryostatin 1 as an activator, not an inhibitor, of PKC.
Which of the following compounds serves as a functional mimic of diacylglycerol (DAG) and is frequently employed experimentally to activate classical Protein Kinase C (PKC) isoforms?
Answer: 12-O-Tetradecanoylphorbol-13-acetate (PMA)
Explanation: PMA is a potent phorbol ester that mimics DAG, effectively activating conventional and novel PKC isoforms in experimental settings.
Which of the following agents is identified in the source material as a potential therapeutic for peripheral diabetic nephropathy, functioning as a Protein Kinase C (PKC) inhibitor?
Answer: Ruboxistaurin
Explanation: Ruboxistaurin is a PKC inhibitor that has been investigated for its potential benefits in treating diabetic nephropathy.
What is the approved medical indication for Ingenol Mebutate, a Protein Kinase C (PKC) activator derived from *Euphorbia peplus*?
Answer: Treatment of actinic keratosis
Explanation: Ingenol mebutate is approved for the topical treatment of actinic keratosis, a precancerous skin condition.
When 12-O-Tetradecanoylphorbol-13-acetate (PMA or TPA) is utilized experimentally in conjunction with ionomycin, what is the resultant combined effect on Protein Kinase C (PKC) activation?
Answer: Ionomycin provides calcium signals, and PMA mimics DAG, together activating certain PKC isoforms.
Explanation: This combination experimentally mimics the signaling events required for activating conventional PKC isoforms by providing both DAG (via PMA) and Ca2+ (via ionomycin).
Which of the following agents is an investigational drug currently undergoing efficacy trials for metastatic uveal melanoma, with Protein Kinase C (PKC) as its therapeutic target?
Answer: Darovasertib
Explanation: Darovasertib is an investigational drug targeting PKC that is being evaluated for its efficacy in treating metastatic uveal melanoma.