RTKS and cells signalling first lecture Flashcards
What is signal transduction?
Signal transduction is the process by which a cell converts an extracellular signal into a response.
What are the three types of chemical cell-to-cell communication?
Autocrine, paracrine, and endocrine.
What is the difference between autocrine and paracrine signaling?
Autocrine signaling is when a cell releases a signal that acts upon itself, while paracrine signaling is when a cell releases a signal that acts upon nearby cells.
What are the four main steps in a signal pathway?
Signal binds to receptor protein, activation of intracellular signal molecules, alteration of target protein, and creation of a response.
What are some examples of signaling molecules?
Peptides/proteins (growth factors, vasoconstrictors), amino acid derivatives (epinephrine, histamine), other small biomolecules (ATP), steroids, prostaglandins, gases (nitric oxide), photons, damaged DNA, odorants, and tastants.
What are the two main types of receptor locations, and what are their general characteristics?
Cell membrane receptors: fast response, for lipophobic ligands that can’t enter the cell (e.g. growth factor receptor).
Cytosolic/nuclear receptors: slower response, for lipophilic ligands that can enter the cell, often regulate gene expression (e.g. steroid hormone receptor).
What are the four types of membrane receptor classes and their examples?
Ion channel-linked receptors (e.g. nAChR)
Receptor-enzyme linked receptors (e.g. EGFR)
G-protein coupled receptors (e.g. Angiotensin R)
Integrin receptors (e.g. Integrin αIIbβ3)
What are the main components involved in signal transduction?
Membrane receptor, protein, amplifier enzymes, second messenger molecules, protein kinases, increasing intracellular calcium, phosphorylated proteins, and calcium-binding proteins.
How do pathways amplify the signal?
Through enzyme cascades and signal amplification during relay, a small signal can produce a large cell response.
What is the role of EGFR in the growth factor pathway?
EGFR, or epidermal growth factor receptor, is a receptor tyrosine kinase that binds to specific growth factors, leading to the activation of downstream signaling pathways such as MAPK/ERK and PI3K/Akt.
What is the Wnt pathway?
The Wnt pathway is a signaling pathway involved in cell proliferation, differentiation, and migration. It plays a crucial role in embryonic development and tissue homeostasis.
What is the Hedgehog pathway?
The Hedgehog pathway is a signaling pathway that regulates cell differentiation, proliferation, and tissue patterning during embryonic development and tissue repair.
What is the Akt/mTOR pathway?
The Akt/mTOR pathway is a signaling pathway that regulates cell growth, proliferation, and survival. It is often dysregulated in cancer and other diseases.
What is the Jak/Stat pathway?
The Jak/Stat pathway is a signaling pathway involved in immune response, cell proliferation, and differentiation. It is activated by cytokines, such as interleukins, and plays a key role in inflammation and immune regulation.
How do cells communicate with each other during signal transduction?
Cells communicate with each other during signal transduction by releasing signaling molecules, which bind to specific receptors on the target cell and trigger a response.
How do cells maintain intracellular homeostasis through signal transduction?
Cells maintain intracellular homeostasis through signal transduction by responding to changes in their environment and regulating various cellular processes such as nutrient uptake, energy production, and gene expression.
How does autocrine signaling work?
In autocrine signaling, a cell releases signaling molecules that bind to receptors on its own surface, triggering a response within the same cell.
How does paracrine signaling work?
In paracrine signaling, a cell releases signaling molecules that diffuse through the extracellular space and bind to receptors on nearby cells, triggering a response in the target cells.
How does endocrine signaling work?
In endocrine signaling, a cell releases signaling molecules (hormones) into the bloodstream, which are then transported to distant target cells, where they bind to specific receptors and trigger a response.
What happens when a signal molecule binds to a receptor protein?
When a signal molecule binds to a receptor protein, it triggers a conformational change in the receptor, which activates intracellular signal molecules.
How do intracellular signal molecules alter target proteins?
Intracellular signal molecules can alter target proteins by adding or removing phosphate groups, binding to specific domains, or promoting conformational changes, which ultimately modulate their activity.
How do peptides/proteins function as signaling molecules?
Peptides/proteins, such as growth factors and vasoconstrictors, can bind to specific receptors on target cells, initiating signal transduction pathways that regulate various cellular processes
What are the roles of amino acid derivatives as signaling molecules?
Amino acid derivatives, such as epinephrine and histamine, function as signaling molecules by binding to specific receptors on target cells, modulating cellular responses like inflammation, vasodilation, or the fight-or-flight response.
How do steroids function as signaling molecules?
Steroids are lipophilic molecules that can pass through the cell membrane and bind to intracellular or nuclear receptors. Upon binding, they can modulate gene expression and regulate various cellular processes, such as growth, development, and metabolism.
What is the role of prostaglandins as signaling molecules?
Prostaglandins are lipid-derived signaling molecules that play crucial roles in various physiological processes, including inflammation, vasodilation, blood clotting, and pain perception. They exert their effects by binding to specific membrane-bound receptors on target cells.
How do gases like nitric oxide function as signaling molecules?
Gases like nitric oxide can function as signaling molecules by diffusing across cell membranes and directly interacting with intracellular target proteins, such as soluble guanylyl cyclase, which modulates cGMP levels and triggers a cellular response.
What is the difference between lipophobic and lipophilic ligands?
Lipophobic ligands are water-soluble and cannot pass through the cell membrane, while lipophilic ligands are fat-soluble and can easily diffuse through the membrane.
How do fast-response membrane receptors work?
Fast-response membrane receptors, like ion channels or receptor-enzyme linked receptors, initiate rapid cellular responses upon ligand binding by changing their conformation or activating intracellular enzymes.
How do slower-response cytosolic/nuclear receptors work?
Slower-response cytosolic/nuclear receptors, like steroid hormone receptors, regulate gene expression by binding to lipophilic ligands that enter the cell, forming a complex that translocates to the nucleus and interacts with specific DNA sequences.
How do ion channel-linked receptors function?
Ion channel-linked receptors function by undergoing a conformational change upon ligand binding, opening or closing an ion channel that allows ions to pass through the cell membrane, thus altering the membrane potential and causing a cellular response.
How do receptor-enzyme linked receptors function?
Receptor-enzyme linked receptors function by activating an intracellular enzyme upon ligand binding, triggering a downstream cascade of signaling events that lead to a cellular response.
How do G-protein coupled receptors function?
G-protein coupled receptors function by activating an intracellular G protein upon ligand binding, which then interacts with other signaling molecules, such as enzymes or ion channels, to modulate cellular responses.
How do integrin receptors function?
Integrin receptors function by binding to extracellular matrix components and interacting with intracellular proteins, such as the actin cytoskeleton, to modulate cellular adhesion, migration, and signaling.
What are amplifier enzymes and how do they function in signal transduction?
Amplifier enzymes are intracellular enzymes that catalyze the production of multiple second messenger molecules upon activation by a signaling pathway. They amplify the signal by rapidly increasing the concentration of second messengers inside the cell.
What is the role of protein kinases in signal transduction?
Protein kinases are enzymes that phosphorylate target proteins in response to signaling events, which can activate or deactivate the target proteins, modulating their function and ultimately leading to a cellular response.
How does increasing intracellular calcium contribute to signal transduction?
Increasing intracellular calcium levels can activate calcium-binding proteins, such as calmodulin, which in turn can modulate the activity of various target proteins, including ion channels, enzymes, and transcription factors, ultimately leading to a cellular response.
What is an enzyme cascade?
An enzyme cascade is a series of sequential reactions involving enzymes, where the product of one reaction serves as the substrate for the next reaction. This cascade effect can amplify a signal, leading to a larger cellular response.
How does signal amplification occur during relay in signal transduction pathways?
Signal amplification during relay occurs when each signaling molecule in the pathway activates multiple downstream molecules, creating a cascade effect that leads to a large cellular response from a small initial signal.
What is the purpose of signal amplification in cell signaling?
Signal amplification in cell signaling ensures that a small extracellular signal, such as the binding of a single ligand to a receptor, can produce a robust and coordinated cellular response by activating multiple intracellular signaling molecules and pathways.
What are proto-oncogenes?
Proto-oncogenes are normal genes that, when mutated or overexpressed, can contribute to the development of cancer. They play a role in regulating cell growth, differentiation, and survival.
How can signaling proteins contribute to cancer development?
Signaling proteins can contribute to cancer development when mutations or dysregulation in their function lead to uncontrolled cell growth, survival, or proliferation, resulting in tumor formation.
What are serine/threonine kinases?
Serine/threonine kinases are enzymes that phosphorylate serine and threonine residues on target proteins, playing a role in regulating various cellular processes, including signal transduction, cell division, and apoptosis.
What is the role of Raf kinases in cell signaling?
Raf kinases are serine/threonine kinases that play a crucial role in the MAPK/ERK signaling pathway, which regulates cell growth, differentiation, and survival.
What are non-receptor tyrosine kinases?
Non-receptor tyrosine kinases are intracellular enzymes that phosphorylate tyrosine residues on target proteins, playing a role in various signaling pathways that regulate cell growth, survival, and differentiation.
What is the role of Src kinases in cell signaling?
Src kinases are non-receptor tyrosine kinases that regulate various cellular processes, including cell adhesion, migration, and proliferation. They are involved in multiple signaling pathways and have been implicated in cancer development.
What is the role of Abl kinases in cell signaling?
Abl kinases are non-receptor tyrosine kinases that play a role in regulating cell growth, survival, and differentiation. They have been implicated in the development of certain types of leukemia, such as chronic myeloid leukemia (CML).
What are GTP-binding proteins?
GTP-binding proteins, also known as G-proteins, are intracellular signaling molecules that bind to guanosine triphosphate (GTP) and play a role in various signal transduction pathways, including those involved in cell growth, survival, and differentiation.
What is the role of Ras proteins in cell signaling?
Ras proteins are small GTP-binding proteins that function as molecular switches in various signaling pathways, including the MAPK/ERK and PI3K/Akt pathways. Mutations in Ras genes are frequently found in human cancers, contributing to uncontrolled cell growth and survival.
___________is a protein that stimulates cell growth, proliferation, and differentiation by binding to its receptor, It plays a crucial role in processes such as wound healing and tissue repair.
Epidermal Growth Factor (EGF)
___________is a family of growth factors involved in various biological processes, including cell growth, development, wound healing, and angiogenesis. it exerts their effects by binding to __________ receptors, which are receptor tyrosine kinases.
Fibroblast Growth Factor (FGF) and FGF
COMPLETE THE MISSING STUFF AND WORK OUT WHAT THE REACTION WILL GIVE BASED ON YOU KNOWLEGDE
COMPLETE THE IMAGE AND WHAT IS IT ABOUT?
WHAT DOEES EACH MIDLE ICON DO?
WHAT DOES EACH LINE BIND TO? COMP;LETE THE IMAGE
EXPLAINING THIS IMAGE
What is the general concept depicted in the image
illustrates the binding of docking proteins to the intracellular domain of the platelet-derived growth factor (PDGF) receptor following its activation. The image shows specific tyrosine kinase domains, the SH2 and SH3 domains, and the recruitment of signaling molecules such as PI-3 kinase regulatory subunit, GTPase-activating protein (GAP), and phospholipase C-gamma (PLCγ).
How does the binding of docking proteins to RTKs occur?
The binding of docking proteins to RTKs, such as the PDGF receptor, is sequence-specific and occurs via interactions between the SH2 domains of the docking proteins and the phosphorylated tyrosine residues on the activated RTK. This interaction enables the recruitment and activation of downstream signaling molecules.
What is the role of SH2 and SH3 domains in RTK signaling?
SH2 and SH3 domains are found in many signaling proteins and serve as interaction modules that help facilitate the assembly of signaling complexes. SH2 domains specifically recognize and bind to phosphorylated tyrosine residues on activated RTKs, while SH3 domains typically bind to proline-rich sequences in target proteins.
What are the functions of the PI-3 kinase regulatory subunit, GTPase-activating protein (GAP), and phospholipase C-gamma (PLCγ)?
PI-3 kinase regulatory subunit: A component of the PI3K complex that plays a role in the activation of the PI3K/Akt signaling pathway, which regulates cell growth, survival, and metabolism.
GTPase-activating protein (GAP): Regulates the activity of small GTPases, such as Ras, by promoting the conversion of active GTP-bound forms to inactive GDP-bound forms, thus modulating various cellular processes.
Phospholipase C-gamma (PLCγ): An enzyme that cleaves phospholipids to generate inositol trisphosphate (IP3) and diacylglycerol (DAG), which serve as second messengers to activate downstream signaling pathways, such as the protein kinase C (PKC) pathway.
Why is the sequence-specific binding of docking proteins to activated RTKs important?
Sequence-specific binding of docking proteins to activated RTKs ensures the proper recruitment and activation of downstream signaling molecules, leading to the precise regulation of cellular processes. Dysregulation of these interactions can result in aberrant signaling and contribute to the development of diseases, including cancer.
Why is the sequence-specific binding of docking proteins to activated RTKs important?
Sequence-specific binding of docking proteins to activated RTKs ensures the proper recruitment and activation of downstream signaling molecules, leading to the precise regulation of cellular processes. Dysregulation of these interactions can result in aberrant signaling and contribute to the development of diseases, including cancer.
EXPLAIN EACH TERM, WHAT THEY DO?
Non-receptor TKs such as Src?
Phospholipase Cγ (PLCγ):
Phosphatidylinositol 3’ kinase (PI 3-kinase):
SHP2 tyrosine phosphatase:
GTPase activating protein
Nck2:
Non-receptor TKs such as Src: Kinases that are not part of a receptor but still play crucial roles in various signaling pathways.
Phospholipase Cγ (PLCγ): An enzyme that breaks down phosphatidylinositol (4,5) bisphosphate (PI4,5P2) into second messengers IP3 and DAG.
Phosphatidylinositol 3’ kinase (PI 3-kinase): An enzyme that phosphorylates PI4,5P2 to generate the second messenger PI3,4,5P3.
SHP2 tyrosine phosphatase: An enzyme that dephosphorylates phosphorylated tyrosine residues on RTKs.
GTPase activating protein: A protein that inactivates p21Ras-GTP, thus modulating small GTPase activity.
Nck2: A protein involved in the regulation of the cytoskeleton.
What is the purpose of attenuation and termination in the context of RTK activation?
Attenuation and termination help in stopping or reducing the intensity of RTK activation, thus maintaining cellular balance and preventing excessive signaling.
What is ligand displacement, and how does it contribute to the regulation of RTK activation?
Ligand displacement is the process where one ligand is replaced by another, potentially modulating receptor activation. It can change the signaling outcome by altering the strength or duration of RTK activation.
How do endocytosis and degradation contribute to the termination of RTK signaling?
Endocytosis and degradation involve the internalization and breakdown of receptors by the cell, effectively terminating the signal by removing the receptor from the cell membrane and preventing further signaling.
What is the role of Protein Tyrosine Phosphatases (PTP) in the regulation of RTK activation?
PTPs are enzymes that remove phosphate groups from phosphorylated tyrosine residues, reversing the activation of RTKs and contributing to the termination of signaling.
How does Protein Kinase C (PKC) help regulate RTK activation?
PKC is a family of enzymes that play a role in the regulation of various cellular processes, including the termination of RTK activation. They can modulate signaling pathways downstream of RTKs, thus influencing the overall cellular response.
DRAW OUT EACH STRUCTURE
