MCB lect 1

A cell is the basic structural, functional and biological unit of organisms. They are known to respond to stimuli

They activate or deactivate protein in a cell with response to an extracellular stimuli

Acetylation Methylation Phosphorylation Nitration

<p>autophosphorylation of tyrosine residues (B)</p> Signup and view all the answers

<p>Receptor Tyrosine Kinases. When RTK substrate - which can be either soluble (EGF) or membrane-bound (ephrins) - binds to the ligand binding domain on the extracellular region of the receptor, it results in the dimerization of the RTK and the activation of its kinase domain. this then allows for cross-phosphorylation of the tyrosine residues, known as trans-autophosphorylation. Signalling proteins can then be phosphorylated by these residues to relay the signal into the cell's interior.</p> Signup and view all the answers

<p>60 genes, classified into 20 subfamilies (B)</p> Signup and view all the answers

<p>tyrosine (only one involved in cell signalling), serine, and threonine. phosphorylation takes place on the hydroxyl group</p> Signup and view all the answers

<p>To bind phospho-tyrosine residues (D)</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

<p>SH2 = Binds to phospho-tyrosine residues SH3 = Binds to proline-rich regions c-Cbl = Inhibitor of RTK signaling RAS = Signaling molecule activated by RTK</p> Signup and view all the answers

<p>due to the large size of the ligand, binding has to be extracellular and upon binding to the receptor, it undergoes a conformational change, which results in autophosphorylation of the intracellular tyrosine domains</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>overall same, ligand binding, dimerization, phosphorylation and signal cascade</p> Signup and view all the answers

<p>extracellular cysteine domain = can be easily modified in response to oxidative stress kinase insert region = break in kinase domain, alters its activity tryosine kinase domain = autophosphorylation immunoglobulin like domain = has a role in immune response</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<ol> <li>LIGAND BINDING (IGF): dimerization, trans autophosphorylation</li> <li>CONFORMATIONAL CHANGE (EGF): conformational change exposing the kinase domain resulting in phosphorylation</li> </ol> Signup and view all the answers

<p>to investigate the function of receptor tyrosine kinases by examining the role of dimerization without the activation of the kinase.</p> Signup and view all the answers

<p>Receptor dimerization is crucial for activating signaling pathways, allowing researchers to analyze the effects of dimerization on downstream responses.</p> Signup and view all the answers

<p>difficulty determining specificity, overactivation of signalling pathway etc</p> Signup and view all the answers

<p>may result in impaired signaling, preventing the activation of downstream pathways necessary for cell proliferation and differentiation.</p> Signup and view all the answers

<p>when one monomer has the tyrosine kinase domain, but the other doesn't (mutant). so upon ligand binding and dimerization, no cross-phosphorylation takes place</p> Signup and view all the answers

<p>if a cell is high enough in the mutant RTK, it can hinder growth and survival. enough of the mutant can completely turn off signalling.</p> Signup and view all the answers

<p>True (A)</p> Signup and view all the answers

<p>it contributes in 2 ways:</p> <ol> <li>increases the kinase activity of the enzyme</li> <li>creates docking sites with high affinity for intracellular signalling molecules</li> </ol> Signup and view all the answers

<ol> <li>getting phosphorylated on the tyrosine domain</li> <li>binding resulting in a conformational change</li> <li>just by being close in proximity to the next protein in the signalling pathway</li> </ol> Signup and view all the answers

<p>SH2/PTB- these bind to the phospho-tryosine domains, linking adaptor proteins to the RTK and other signalling proteins SH3- these bind to proline-rich domains, linking adaptor protein to the membrane and other signalling proteins</p> Signup and view all the answers

<p>c-Cbl functions as an inhibitor by monoubiquitylating RTKs, leading to either their endocytosis (recycling) or degradation</p> Signup and view all the answers

<p>Monoubiquitylation leads to two possible outcomes by targeting RTKs to clathrin-coated vesicles: they can either be degraded by the lysosome or recycled back to the plasma membrane. While polyubiquitylation directly targets proteins for degradation via the proteasome.</p> Signup and view all the answers

<p>Clathrin-coated vesicles are essential for the endocytosis of monoubiquitylated RTKs, facilitating their transport to lysosomes for degradation or their recycling back to the plasma membrane.</p> Signup and view all the answers

<p>c-Cbl negatively regulates the RTK signaling pathway by promoting monoubiquitylation, leading to reduced signaling.</p> Signup and view all the answers

<p>Endocytosis allows the receptor to be internalized.</p> Signup and view all the answers

<p>The receptor/ligand complex is targeted to the lysosome for degradation.</p> Signup and view all the answers

<p>A change in pH causes the ligand to dissociate from the receptor, allowing recycling.</p> Signup and view all the answers

<p>Receptor downregulation reduces signaling response while allowing the receptor to be recycled, whereas termination involves degradation.</p> Signup and view all the answers

<p>This downregulates the signal. Allows the receptor to be recycled back to the plasma membrane, for reactivation.</p> Signup and view all the answers

<p>It leads to prolonged RTK signaling, which can result in cancer.</p> Signup and view all the answers

<p>NGF ligands can travel in an endosome along the nerve axon to signal to the cell body.</p> Signup and view all the answers

<p>Endocytosis can potentially lead to the transport of signal molecules, allowing continued signaling rather than stop.</p> Signup and view all the answers

<p>2, overall 2, 1, 2 phosphorylation sites</p> Signup and view all the answers

<p>PI3K (C)</p> Signup and view all the answers

<p>GAP (D)</p> Signup and view all the answers

<p>Phospholipase C gamma (A)</p> Signup and view all the answers

<p>Upon the binding of insulin to its receptor, the receptor monomers dimerize, initiating the transautophosphorylation of their tyrosine kinase domains. These phosphorylated domains then serve as docking sites for IRS1, which subsequently recruits the adaptor protein GRB2 through its SH2 domain. GRB2, equipped with SH3 domains, facilitates the interaction with additional signaling proteins, thus triggering a cascade of cellular responses. PH domains play a crucial role in linking the protein complex to the plasma membrane and cytoskeleton by binding to inositide lipids and scaffold proteins, respectively. Activation of the RAS pathway is mediated by the SOS protein, which functions as a RAS-specific guanine nucleotide exchange factor (RAS-GEF).</p> Signup and view all the answers

<p>Ras-GEFs promote the exchange of GDP for GTP, activating Ras, while Ras-GAPs accelerate the hydrolysis of GTP to GDP, inactivating Ras.</p> Signup and view all the answers

<p>Lipid groups anchor Ras to the cytoplasmic face of the plasma membrane, allowing it to relay signals from cell-surface receptors.</p> Signup and view all the answers

<p>Ras acts as a molecular switch by cycling between active GTP-bound and inactive GDP-bound states, thus regulating signal transduction pathways that influence cell behavior.</p> Signup and view all the answers

<p>Ras signaling can activate transcription factors that lead to changes in gene expression, promoting processes such as cell proliferation and differentiation.</p> Signup and view all the answers

<p>When an RTK is activated, it enables the cell to move by linking to the cytoskeleton and alters gene expression.</p> Signup and view all the answers

<p>Boss, membrane bound ligand, binds to the receptor resulting in dimerization and transautophosphorylation of the RTK, the adaptor protein DRK containing the SH2 domain docks in these phospho-tyrosine domains. DRK also contains SH3 domains which is used to bind to SOS protein containing RAS-GEF and so once active it facilitates for the exchange of GDP with GTP</p> Signup and view all the answers

<p>False (B)</p> Signup and view all the answers

A small protein region (domain) that specifically recognizes and binds to proline-rich sequences in other proteins, often involved in signaling pathways.

A small protein region (domain) that specifically recognizes and binds to phosphorylated tyrosine residues on other proteins, commonly involved in signaling pathways.

A signaling molecule that binds to a receptor tyrosine kinase (RTK), triggering a cascade of downstream events.

A type of protein kinase that adds phosphate groups to tyrosine residues on other proteins, often initiating signaling pathways.

The process by which a cell takes in molecules from its surroundings by engulfing them in membrane-bound vesicles.

A type of protein degradation pathway that breaks down proteins into smaller peptides, mediated by a complex called the proteasome.

The addition of a single ubiquitin molecule to another protein, often leading to changes in its function or localization within the cell.

A protein that inhibits signaling pathways by promoting the degradation of activated receptor tyrosine kinases (RTKs).

Adaptor proteins are signaling proteins that do not have their own SH2 domains. They bind to activated RTKs using their SH2 domains and recruit other signaling proteins to the complex.

Guanine exchange factor (GEF) is a type of protein that activates Ras, a key signaling molecule. GEFs work by exchanging GDP (inactive form) for GTP (active form) on Ras.

Ras is a small GTPase protein involved in a wide range of cellular processes, including cell growth, differentiation, and proliferation. It acts as a molecular switch, cycling between an active GTP-bound state and an inactive GDP-bound state.

A signaling pathway that begins with the activation of a receptor tyrosine kinase (RTK) and leads to the activation of Ras and the MAPK pathway.

A type of protein kinase that plays a central role in regulating cell growth, differentiation, and survival. It acts as a downstream effector of the Ras signaling pathway.

In the context of the Drosophila eye development, Drk is the receptor tyrosine kinase (RTK) that's responsible for receiving signals from the BOSS ligand. Mutating its SH3 domain would prevent it from recruiting Sos, a Ras-GEF., resulting in impaired Ras activation and thus, eye development.

Receptor-mediated endocytosis allows for the removal of signaling molecules and receptors from the cell surface. This process involves internalization of the receptor-ligand complex into an endosome, where the ligand dissociates from the receptor due to a change in pH. The receptor can then be recycled back to the plasma membrane, or be targeted to the lysosome for degradation.

Mutations that inactivate c-Cbl, a protein involved in receptor tyrosine kinase (RTK) downregulation, can lead to prolonged RTK signaling, which contributes to uncontrolled cell growth and development of cancer.

While receptor tyrosine kinase (RTK) endocytosis usually leads to decreased signaling, there are exceptions. For example, nerve growth factor (NGF) bound to its RTK can travel within endosomes along the nerve axon to signal to the cell body, enabling signaling over long distances.

The SH2 domain binds to phosphorylated tyrosine residues, while the SH3 domain interacts with proline-rich regions on other proteins. These interactions form a protein scaffold, facilitating the assembly of signaling complexes.

Insulin-like growth factor receptor (IGFR) dimerizes upon binding to its ligand, resulting in trans-autophosphorylation. This phosphorylation enhances kinase activity and leads to further phosphorylation of tyrosine residues, initiating a signal transduction cascade.

Inhibition of c-Cbl, a negative regulator of the RTK pathway, leads to increased RTK signaling. This can promote uncontrolled cell growth, ultimately contributing to cancer development.

A mutant form of a receptor that can dimerize, but cannot phosphorylate. This mutant is used to study the role of receptor dimerization in RTK signaling.

The process of delivering an artificial construct (e.g., a mutant gene) into cells, allowing the cells to express the introduced genetic material.

The ability of a receptor tyrosine kinase (RTK) to form a dimer (two subunits) upon ligand binding is essential for its activation.

This is a key process for studying the role of dimerization in RTK signaling. By creating a mutant receptor that can only dimerize but not activate downstream signaling, researchers can isolate the effects caused purely by dimerization.

Introducing a mutated RTK that can dimerize but not phosphorylate into cells allows researchers to determine the role of dimerization in RTK signaling. If the mutant still activates some signaling events, it suggests that dimerization alone is sufficient for those events.

c-Cbl is a protein that inhibits RTK signaling by adding a single ubiquitin molecule (monoubiquitylation) to the RTK. This promotes endocytosis and degradation of the RTK, effectively turning down the signaling pathway.

Monoubiquitylation of an RTK leads to its internalization into a clathrin-coated vesicle, which can either be recycled back to the plasma membrane or sent to the lysosome for degradation.

Polyubiquitylation involves the addition of multiple ubiquitin molecules to a protein, typically targeting it for degradation by the proteasome.

c-Cbl acts as an inhibitor of RTK signaling because it promotes the degradation of activated RTKs, effectively turning off the signaling pathway.

Some proteins that bind to activated RTKs via SH2 domains do not necessarily continue the signal. Instead, they can act as negative regulators, like c-Cbl, and promote the deactivation of the RTK.

A process by which a cell reduces its response to a signal by removing receptors from the cell surface.

A process where a cell permanently stops responding to a signal by degrading the receptor-ligand complex in the lysosome.

Change in pH within an endosome that triggers the dissociation of a ligand from its receptor, enabling the receptor to be recycled back to the cell surface.

A type of protein degradation pathway that involves breaking down proteins into smaller peptides within lysosomes.

Some RTK endocytosis doesn't lead to decreased signaling. Nerve growth factor (NGF) bound to its RTK can travel in an endosome along the nerve axon to signal to the cell body.

Mutations that inactivate c-Cbl, a protein that helps regulate RTK signaling, lead to prolonged RTK signaling, which can contribute to cancer.

c-Cbl promotes the degradation of activated RTKs, helping to regulate signaling.

The process by which a cell takes in molecules from its surroundings by engulfing them in membrane-bound vesicles.

Ras, Rho, and other related proteins are small GTPases that act as molecular switches, cycling between an active GTP-bound state and an inactive GDP-bound state.

Ras proteins are anchored to the plasma membrane by covalently attached lipid groups, which are like small 'handles' that attach them to the inner surface of the cell membrane.

Ras-GEFs activate Ras by facilitating the exchange of GDP for GTP, promoting the active state. Ras-GAPs inactivate Ras by triggering the hydrolysis of GTP to GDP, returning it to the inactive state.

Ras is a key signaling protein involved in relaying signals from cell surface receptors to the nucleus, ultimately influencing gene expression and cellular processes like proliferation and differentiation.

Ras signaling contributes to two key outcomes: cell movement by linking to the cytoskeleton and changes in gene expression, which ultimately drives growth and development.

Paris