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Introduction to Chemical Signaling
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Today we will discuss chemical signaling, which is vital for communication between cells in multicellular organisms. Can anyone tell me why this communication is important?
Maybe to help cells respond to changes in their environment?
Exactly! Cell signaling allows for coordination of development, maintenance of homeostasis, and other crucial functions. We have several modes of signaling: autocrine, paracrine, endocrine, and juxtacrine. Let's start with autocrine. Can anyone explain what that means?
I think it means a cell signals itself, like when a tumor cell produces a growth factor that stimulates its own growth.
Right! In autocrine signaling, the cell produces a signal that binds to its own receptors. Now, what about paracrine signaling?
That's when signals affect nearby cells, like neurotransmitters in the synaptic cleft.
Correct! Paracrine signaling allows cells to influence their neighbors. Endocrine signaling, on the other hand, involves hormones traveling through the bloodstream to distant targets. Can anyone give an example?
Insulin is a good example since it regulates blood glucose levels throughout the body.
Exactly! And lastly, we have juxtacrine signaling, which requires direct contact between cells. These interactions can lead to significant developmental processes. Letโs remember these modes: 'A' for Autocrine, 'P' for Paracrine, 'E' for Endocrine, and 'J' for Juxtacrine. How about we summarize what we've learned today?
Chemical signaling is critical for cells to communicate. We learned about four signaling modes: autocrine, paracrine, endocrine, and juxtacrine. Keep these definitions and examples in mind as we move forward!
Ligands and Receptors
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Letโs dive deeper into ligands and receptors, as they are key components in signaling pathways. Can someone name a type of ligand?
How about insulin? It's a peptide hormone.
Great! Insulin is a peptide hormone. Other types include steroid hormones like cortisol, and gasotransmitters such as nitric oxide. What do you think receptors do?
Receptors receive signals from these ligands?
Exactly! Receptors bind to specific ligands, triggering a response in the target cell. There are two main types of receptors: cell surface receptors and intracellular receptors. Can anyone give an example of a cell surface receptor?
G-Protein Coupled Receptors (GPCRs) are a good example!
Correct! GPCRs activate G-proteins upon ligand binding. Another example is receptor tyrosine kinases (RTKs). They auto-phosphorylate and interact with various signaling pathways. Can you tell me why this is important?
Because it allows for a cascading effect that amplifies the signal?
Yes! This signal amplification can lead to significant changes in cellular activity. Letโs summarize this key point: Ligands bind to receptors, activating signaling pathways that result in cellular responses. This is central to understanding how chemical signals affect cellular functions.
Signal Transduction Pathways
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Now, letโs explore how signals are transmitted within cells via signal transduction pathways. What would happen when a ligand binds to a receptor?
It probably activates a chain of events inside the cell!
Exactly! One common pathway is the cAMP pathway. Can anyone explain its steps in brief?
First, the G-protein activates adenylate cyclase, converting ATP to cAMP. Then cAMP activates Protein Kinase A.
Well done! This leads to phosphorylating various target proteins. Signal transduction can also utilize second messengers like Caยฒโบ, IPโ, and DAG. Can anyone tell me the significance of second messengers?
They help amplify the signal, right?
Precisely! Signal amplification is crucial for a swift cellular response to stimuli. Lastly, letโs discuss feedback mechanisms. Why is negative feedback important in signaling pathways?
It helps maintain homeostasis by shutting down a pathway when a certain level is reached!
Great point! Feedback mechanisms ensure that responses do not escalate beyond what is necessary. Letโs summarize: Signal transduction pathways convert external signals into cellular responses and often employ second messengers for amplification. Remember the roles of each component!
Specificity of Signaling
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Now that weโve established how signals are transduced, letโs talk about specificity. How do cells ensure that they respond correctly to specific signals?
I guess it has something to do with receptors being specific to certain ligands?
Exactly! Each type of receptor is tailored to specific ligands, which is why specificity is crucial. Can anyone think of how scaffolding proteins play a role here?
They bring different parts of a signaling cascade together for efficient processing?
Yes, scaffolding proteins enhance specificity and speed of the signaling response. In addition, spatial organization within the cell can concentrate signaling components in certain areas. Therefore, understanding affinity and binding properties improves our insight into signaling dynamics. Letโs wrap up: Specificity in signaling ensures that cells accurately interpret and respond to diverse stimuli while maintaining organization through scaffolding proteins.
Summarizing Chemical Signaling
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As we conclude our discussion on chemical signaling, can anyone summarize the main modes of signaling we covered?
We talked about autocrine, paracrine, endocrine, and juxtacrine signaling!
Exactly! And remember, each mode is important for different contexts in cell communication. What did we learn about ligands and receptors?
Theyโre specific to each other and can initiate different pathways inside the cell!
Correct! Ligand-receptor interactions lead to essential cellular responses through signal transduction pathways, which can involve second messengers and amplification. To summarize, what is the significance of specificity in signaling?
Specificity ensures that the right cells respond correctly to signals, using scaffolding proteins and organized parts!
Perfect summary! Chemical signaling is key to how living organisms achieve coordination and functionality. Make sure you review these notes before our next class!
Introduction & Overview
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Quick Overview
Standard
This section explores the intricate chemical signaling mechanisms that enable multicellular organisms to communicate effectively. It discusses various signaling modesโautocrine, paracrine, endocrine, and juxtacrineโand delves into the role of ligands and receptors in signal transduction pathways, including GPCRs, RTKs, and intracellular receptors. The significance of signal amplification and specificity in response to various stimuli is also emphasized.
Detailed
Chemical Signaling Overview
Chemical signaling is crucial for the communication between cells in multicellular organisms, allowing them to react to physiological changes, coordinate developmental processes, and maintain homeostasis. This signaling can happen via several modes: autocrine (where cells signal themselves), paracrine (neighboring cell signaling), endocrine (hormonal signaling over longer distances), and juxtacrine (direct cell contact signaling).
Ligands and Receptors
Ligands referred to as signaling molecules, can be diverse in nature, including peptide hormones like insulin, steroid hormones such as cortisol, and gasotransmitters like nitric oxide. Each ligand interacts with specific receptors on target cells, which can be categorized into two main types:
- Cell Surface Receptors (e.g., G-Protein Coupled Receptors, Receptor Tyrosine Kinases, Ion Channels) that initiate a cascade of intracellular events upon ligand binding.
- Intracellular Receptors (e.g., nuclear hormone receptors) that bind lipid-soluble ligands and modify gene expression directly.
Signal Transduction Pathways
Signal transduction pathways are essential for translating extracellular signals into intracellular responses. For instance, the cAMP pathway activates Protein Kinase A as a downstream effect leading to various cellular responses, while the PI pathway generates second messengers like IPโ and DAG affecting calcium signaling and protein kinase activation.
Amplification and Specificity
The sharp response to minimal ligand presence highlights the importance of signal amplificationโone ligand-receptor interaction can activate multiple downstream signals, ensuring a robust response. Additionally, scaffolding and anchoring proteins help concentrate and organize signaling components, enhancing specificity.
In conclusion, understanding chemical signaling pathways is key to revealing how cells communicate and coordinate functions within a multicellular organism, ultimately contributing to their growth, survival, and adaptation.
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Audio Book
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Overview of Cell-to-Cell Communication
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- Overview of Cell-to-Cell Communication
- Importance: Chemical signaling allows cells to respond to changes in the internal and external environment, coordinate development, maintain homeostasis, and mount immune responses.
- Modes of Signaling:
- Autocrine: Cell secretes signaling molecule that binds to receptors on its own surface (e.g., some growth factors in cancer cells).
- Paracrine: Signal released by one cell influences neighboring cells (e.g., neurotransmitters in synaptic cleft, growth factors in tissue).
- Endocrine: Hormones secreted into bloodstream travel to distal target cells (e.g., insulin, cortisol).
- Juxtacrine (ContactโDependent): Signaling molecule remains on cell surface; adjacent cellโs receptor binds directly (e.g., Notch signaling).
Detailed Explanation
In this chunk, we explore how cells communicate with each other through chemical signals, which is essential for many biological processes. Chemical signaling is vital because it helps cells respond to changes in their surroundings, manage development, keep the body in balance (homeostasis), and trigger immune responses against pathogens. There are four main types of signaling:
- Autocrine signaling occurs when a cell produces a signal that binds to receptors on its own surface; this can affect its own functions. An example is how some cancer cells produce growth factors that stimulate their own growth.
- Paracrine signaling involves signals affecting nearby cells; for instance, neurotransmitters are released from one neuron and affect another neuron right next to it.
- Endocrine signaling sends hormones into the bloodstream, allowing signals to reach distant cells. For example, insulin is released from the pancreas and travels throughout the body to regulate blood sugar levels.
- Juxtacrine signaling is direct and requires cell-to-cell contact, such as Notch signaling where a signal from one cell directly interacts with a neighboring cell's receptor to initiate a response.
Examples & Analogies
Think of chemical signaling like a network of walkie-talkies used by a group of emergency responders. When one responder (cell) detects a fire in a building (environmental change), they call out (send a chemical signal) to nearby responders (neighboring cells) to alert them. If there are more than one emergency units (like hormonal signals) that need to be informed, they broadcast their message to a larger area, even reaching those further away (endocrine signaling). Sometimes, they even send messages to themselves to prepare for the actions they need to take (autocrine). Juxtacrine signaling is like one responder directly handing a note to another, needing to be physically close to communicate.
Ligands and Receptors
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- Ligands and Receptors
- Ligands (Signaling Molecules)
- Peptide/Protein Hormones: Insulin, glucagon, growth hormone.
- Steroid Hormones: Cortisol, estrogen, testosterone (lipidโsoluble, derived from cholesterol).
- Amino Acid Derivatives: Thyroid hormones, catecholamines (epinephrine, norepinephrine).
- Gasotransmitters: Nitric oxide (NO), carbon monoxide (CO).
- Lipid Mediators: Prostaglandins, leukotrienes (eicosanoids).
- Receptors
- Cell Surface Receptors (Membrane Proteins)
- G-Protein Coupled Receptors (GPCRs): Sevenโtransmembrane ฮฑโhelices. Ligand binding activates heterotrimeric G protein (Gฮฑ + Gฮฒฮณ). Gฮฑ exchanges GDP for GTP, dissociates, and modulates downstream effectors (e.g., adenylate cyclase, phospholipase C).
- Receptor Tyrosine Kinases (RTKs): Single transmembrane segment. Ligand binding induces dimerization/oligomerization, autophosphorylation of intracellular tyrosine residues.
- Ion Channel Receptors (LigandโGated Channels): Open or close in response to ligand binding (e.g., nicotinic acetylcholine receptor, GABAA receptor). Fast synaptic transmission.
- Cytokine Receptors (JAK-STAT Pathway): Ligand binding (e.g., interleukins, interferons) brings receptors together, activating associated Janus kinases (JAKs) which phosphorylate STAT proteins, enabling them to translocate to the nucleus and modulate gene expression.
- Intracellular Receptors (Cytosolic/Nuclear)
- For lipidโsoluble ligands (steroid hormones, thyroid hormones). Ligand diffuses across membrane, binds receptor in cytosol or nucleus. Ligandโreceptor complex undergoes conformational change, binds to specific DNA sequences (hormone response elements), modulating transcription. Example: Glucocorticoid receptor binds glucocorticoid, translocates to nucleus, regulates gluconeogenesis genes.
Detailed Explanation
This section discusses the types of signaling molecules known as ligands and the receptors they bind to in order to initiate a response in cells. Ligands can be various types of molecules, including hormones and neurotransmitters, which can be protein-based, steroid hormones, or derived from amino acids. For example, insulin is a protein hormone that helps regulate blood sugar levels, while cortisol, a steroid hormone, influences metabolism and immune response.
Receptors can be broadly categorized based on their location and function. Many receptors are located on the cell surface, such as G-Protein Coupled Receptors (GPCRs), which play a role in numerous signaling pathways by activating a G protein when a ligand binds. Other types of cell surface receptors include Receptor Tyrosine Kinases (RTKs) which change shape and become active upon ligand binding, initiating signaling cascades inside the cell. There are also intracellular receptors that bind lipid-soluble molecules that can cross the cell membrane; these ligands bind to receptors in the cytoplasm or nucleus and directly alter gene expression by modulating transcription.
Examples & Analogies
Imagine ligands and receptors as keys and locks. The ligands are like keys that fit into specific locks (the receptors) on the doors of different rooms (cells) in a house (the body). When you insert the right key (ligand) into the keyhole (receptor), it opens the door, allowing you to enter, just as the binding of a ligand to its receptor activates a series of cellular responses (analogous to entering a room). Just as there can be many different keys for different rooms, there are many types of ligands and receptors, each designed to unlock specific pathways and functions in our cells.
Signal Transduction Pathways
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- Signal Transduction Pathways
- cAMP Pathway (GPCR-Mediated)
- Adenylate Cyclase Activation: Gฮฑs (stimulatory) subunit (bound to GTP) activates adenylate cyclase, converting ATP โ cyclic AMP (cAMP).
- Protein Kinase A (PKA) Activation: cAMP binds regulatory subunits of PKA โ catalytic subunits released โ phosphorylate target proteins (enzymes, transcription factors).
- Example: In the liver, glucagon binds GPCR โ Gฮฑs activates adenylate cyclase โ โ cAMP โ PKA activation โ phosphorylation of phosphorylase kinase โ activation of glycogen phosphorylase โ glycogen breakdown.
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Termination:
- GTPase Activity of Gฮฑs: Intrinsic hydrolysis of GTP โ GDP, re-associating with Gฮฒฮณ, terminating signal.
- Phosphodiesterases (PDEs): Convert cAMP โ AMP, lowering cAMP levels.
- Phosphatidylinositol (PI) Pathway (GPCRs Coupled to Gq)
- Phospholipase C-ฮฒ (PLC-ฮฒ) Activation: Gฮฑq (bound to GTP) activates PLC-ฮฒ.
- PIPโ Cleavage: PLC-ฮฒ hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIPโ) into:
- Inositol 1,4,5-trisphosphate (IPโ): Diffuses into cytosol, binds IPโ receptors on endoplasmic reticulum โ release of Caยฒโบ into cytosol.
- Diacylglycerol (DAG): Remains in membrane, along with Caยฒโบ, activates Protein Kinase C (PKC).
- Caยฒโบ as Second Messenger: Elevated cytosolic Caยฒโบ can bind calmodulin (CaM) โ Caยฒโบ/CaM complex activates CaMโdependent kinases (e.g., CaMK).
- Termination: Caยฒโบ pumped back into ER (via SERCA pumps) or out of cell (via plasma membrane Caยฒโบ ATPases), DAG degraded by DAG kinases.
- Receptor Tyrosine Kinase (RTK) Pathways
- Ras/MAPK Cascade:
- Ligand (e.g., epidermal growth factor [EGF], platelet-derived growth factor [PDGF]) binds RTK โ receptor dimerization and autophosphorylation.
- Adaptor Protein Grb2 binds phosphorylated tyrosine via SH2 domain; Grb2 is constitutively associated with Sos (a guanine nucleotide exchange factor).
- Sos catalyzes GDP โ GTP exchange on Ras (small GTPase), activating Ras.
- Ras-GTP activates Raf (MAPKKK) โ phosphorylates MEK (MAPKK) โ phosphorylates ERK (MAPK).
- ERK translocates to nucleus, phosphorylates transcription factors (e.g., Elk-1), driving cell proliferation or differentiation.
- PI3K/Akt Pathway:
- RTK activation recruits Phosphoinositide 3-Kinase (PI3K) โ converts PIPโ โ Phosphatidylinositol 3,4,5-trisphosphate (PIPโ).
- PIPโ recruits PDK1 and Akt (PKB) to membrane; PDK1 phosphorylates/activates Akt.
- Akt phosphorylates downstream targets to promote cell survival (inhibiting apoptosis), glucose uptake (GLUT4 translocation), protein synthesis (via mTOR).
Detailed Explanation
In this chunk, we delve into how chemical signals are translated into responses within cells through signal transduction pathways. These pathways are crucial in relaying the information from the external environment to the inside of the cell, ultimately leading to a physiological response.
- cAMP Pathway: In this pathway, a signaling molecule binds to a GPCR, activating it. The activated receptor stimulates the Gฮฑs subunit, which activates adenylate cyclase, leading to the conversion of ATP into cyclic AMP (cAMP). cAMP serves as a second messenger that activates Protein Kinase A (PKA), which then phosphorylates target proteins, such as enzymes or transcription factors, ultimately causing changes in cellular activity, like glycogen breakdown in the liver.
- PI Pathway (Phosphatidylinositol): This pathway is initiated when a different type of GPCR activates phospholipase C (PLC). PLC cleaves a specific lipid molecule, PIPโ, generating two products: IPโ and diacylglycerol (DAG). IPโ promotes the release of calcium ions from the endoplasmic reticulum, which aids in further signaling, while DAG remains in the membrane to activate Protein Kinase C (PKC), leading to various downstream effects.
- Receptor Tyrosine Kinase (RTK) Pathways: Here, ligands binding to RTKs facilitate their dimerization (joining of two receptor molecules) and subsequent autophosphorylation (adding phosphate groups to themselves). This activation attracts proteins like Grb2 and Sos, which then activate Ras. The active Ras protein triggers a cascade involving multiple kinases (the MAPK pathway) that ultimately results in cell growth and differentiation. Additionally, some activated RTKs stimulate PI3K, which initiates a pathway that promotes cell survival and metabolic processes.
Examples & Analogies
Picture a bustling office building where communication determines the success of daily operations. When a receptionist receives a call (ligand binding), they pass the information along to the right department (like GPCR activating a G protein). As the information travels down the chain, more and more employees get involved (amplification through second messengers). If the boss (e.g., the activated kinase) decides a task needs to be prioritized, they send out a memo to all employees involved in that project (transcription factor activation). If this message is clear and reaches its destination, everyone knows what to do, just as the cell processes the incoming chemical signals to take action.
Signal Amplification and Specificity
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- Signal Amplification and Specificity
- Amplification: One ligandโreceptor binding event can produce many second messenger molecules (e.g., one activated GPCR can activate multiple G proteins, each G protein can activate adenylate cyclase producing hundreds of cAMP).
- Scaffolding Proteins: Bring sequential kinases into proximity (e.g., KSR scaffold for Ras/MAPK), ensuring specificity and rapid signal relay.
- Anchoring Proteins: (e.g., A-kinase anchoring proteins [AKAPs]) tether PKA to specific subcellular locations, conferring spatial specificity.
- Compartmentalization: Lipid rafts, endosomes, and other microdomains concentrate specific receptors and signaling molecules.
- Negative Feedback and Desensitization: Receptor phosphorylation (e.g., by GRKs [G proteinโcoupled receptor kinases]), ฮฒ-arrestin binding, receptor internalization via endocytosis (clathrinโcoated pits), and downregulation modulate signal duration.
Detailed Explanation
This chunk emphasizes the importance of signal amplification and the mechanisms that provide specificity during cellular signaling. When a single signaling molecule binds to its receptor, it can result in a large cascade of responses. For instance, one activated G protein-coupled receptor (GPCR) can initiate a large number of secondary messengers (like cAMP), amplifying the signal significantly.
To ensure that the correct signals are conveyed efficiently, scaffolding proteins help facilitate interactions between kinases (enzymes that modify other proteins), essentially assembling signaling complexes to enhance specificity. Anchoring proteins, such as A-kinase anchoring proteins (AKAPs), position specific kinases like Protein Kinase A (PKA) near their target substrates, thereby ensuring that their action is localized and precise.
Additionally, compartmentalization, through structures like lipid rafts, allows cells to segregate signaling pathways, preventing crosstalk between different paths. Finally, there are negative feedback mechanisms in play, such as receptor phosphorylation and internalization, that prevent overstimulation of the signaling pathways, allowing cells to temper their responses and adapt quickly to changing conditions.
Examples & Analogies
Imagine a conductor leading a large orchestra. The conductor (ligand) communicates a signal, which is then amplified by the musicians (many second messengers) responding quickly, creating a beautiful symphony (cellular response). The conductor must maintain control and ensure every musician plays the right notes; hence, they use clear signals (scaffolding proteins) to keep sections of the orchestra in sync. If the music gets too loud, the conductor can signal for a softer volume (negative feedback) to keep the performance balanced and harmonious, just as cells regulate their responses to signals.
Definitions & Key Concepts
Learn essential terms and foundational ideas that form the basis of the topic.
Key Concepts
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Chemical Signaling: The process by which cells communicate using signaling molecules.
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Ligands: Molecules that bind to receptors to initiate a signal transduction pathway.
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Receptors: Proteins on or within cells that specifically bind signaling molecules, leading to a response.
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Signal Transduction Pathways: The series of events that lead to cellular responses following ligand-receptor interaction.
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Amplification: The enhancement of a cellular response due to signaling cascades.
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Specificity: The ability of signaling pathways to selectively respond to particular signals.
Examples & Real-Life Applications
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Examples
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Insulin is an example of a peptide ligand that binds to receptors on liver and muscle cells to regulate glucose levels.
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Gastrointestinal hormones signal nearby cells to coordinate digestive functions.
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During an immune response, cytokines are released to communicate between immune cells.
Memory Aids
Use mnemonics, acronyms, or visual cues to help remember key information more easily.
๐ต Rhymes Time
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In a cellular dance, signals do play, / Autocrine, paracrine lead the way, / Endocrine hormones travel far, / Juxtacrine signaling's close as a star.
๐ Fascinating Stories
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Imagine a small town where a mayor (ligand) sends messages (signals) to nearby officials (receptors) to keep the town running smoothly. The mayor can send local notices (paracrine) or broadcast city-wide (endocrine). Thereโs also whispering between two neighbors (juxtacrine), ensuring they stay informed personally.
๐ง Other Memory Gems
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Think of the word 'SIGN' to remember: S for Signal, I for Interaction, G for G-proteins, and N for Nuclear responses.
๐ฏ Super Acronyms
Acronym 'APEJ' stands for Autocrine, Paracrine, Endocrine, Juxtacrine.
Flash Cards
Review key concepts with flashcards.
Glossary of Terms
Review the Definitions for terms.
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Term: Autocrine Signaling
Definition:
A mode of chemical signaling where a cell secretes a signaling molecule that binds to receptors on its own surface.
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Term: Paracrine Signaling
Definition:
A type of signaling where a cell releases signaling molecules that affect nearby cells.
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Term: Endocrine Signaling
Definition:
Signaling involving hormones that are secreted into the bloodstream to act on distant target cells.
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Term: Juxtacrine Signaling
Definition:
Direct cell signaling where the signaling molecule remains on the surface of a cell and interacts with adjacent cells.
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Term: Ligand
Definition:
A molecule that binds to a receptor, triggering a response in the target cell.
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Term: GProtein Coupled Receptors (GPCRs)
Definition:
Membrane receptors that initiate a signaling cascade through G-proteins upon ligand binding.
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Term: Receptor Tyrosine Kinases (RTKs)
Definition:
A class of receptors that become phosphorylated on tyrosine residues, leading to the activation of downstream signaling pathways.
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Term: Second Messenger
Definition:
Intracellular signaling molecules released upon activation of a receptor to amplify the signal.
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Term: Signal Transduction
Definition:
The process by which a chemical signal is transmitted through a cell, leading to a response.
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Term: Scaffolding Proteins
Definition:
Proteins that organize and bring together components of a signaling pathway to enhance specificity and efficiency.
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Term: Amplification
Definition:
The process by which a single signaling event leads to a large-scale cellular response.