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Signal Reception

Signal Reception

Cells have the ability to sense what is going on around them and can react to stimuli from their external environment. In fact, your cells are exchanging millions of signals in the form of chemical signaling molecules right now. Each time you think, eat, read, see, move - every one of those functions is carried out by cells that are talking to each other through the release and reception of chemical messengers.

In the following, we will review the definition, types, and process of cell signaling. Then we will discuss in-depth the first stage of cell signaling, called signal reception. Specifically, we will go into the different types of ligands and receptors involved in signal reception. We will also discuss a specific example.

Cell signaling definition

Cell signaling is the process by which a cell reacts to signals–typically chemical in nature–from its external environment through protein receptors. Cell signaling can take place between cells (intercellular signaling) and within the cell (intracellular signaling).

There are various types of cell signaling. Cells can release ligands that bind to receptors within the same cell. This process is called autocrine signaling. Cells can also communicate with nearby cells in a process called paracrine signaling. Cells in an organism can also receive signals via hormones from cells in distant parts of the body. This process is called endocrine signaling.

Three stages of cell signaling: reception, transduction, and response

Cell signaling has three basic stages:

  1. Signal reception: The cell detects a signal when a signaling molecule called a ligand binds to a receptor protein on the cell surface.

  2. Signal transduction: The ligand reconfigures the receptor protein. The signal is relayed by each molecule changing the next molecule in the pathway.

  3. Cellular response: The signal initiates a specific cellular process.

This article will focus on the first step of cell signaling, signal reception.

Definition of signal reception, ligands, and receptors in biology

Signal reception occurs when a ligand binds to a receptor protein in or on the surface of the plasma membrane. A ligand is a molecule that delivers signals, while a receptor is a molecule to which a ligand binds. Upon binding of the ligand, receptors initiate a physiological response.

Both ligands and receptors have a high level of specificity: typically, a ligand binds to a specific receptor. For example, growth factor receptors bind growth factors (and different subtypes of receptors can bind different types of growth factors), and dopamine receptors bind dopamine. In addition to chemical signals, some receptors can also detect light, heat, pressure, and other external stimuli.

Types of ligands

Ligands come in varying forms and sizes. Here we will discuss hydrophobic ligands and water-soluble ligands.

Small hydrophobic ligands

Small hydrophobic ligands such as steroid hormones directly diffuse through the interior of the plasma membrane and interact with internal or cytoplasmic receptors. Some steroid hormones can also bind to receptors located on the cellular surface.

Steroids are lipids with four fused rings on their hydrocarbon skeleton, which are connected to various functional groups depending on the kind of steroid. Testosterone (the male sex hormone), estradiol (the female sex hormone), and cholesterol (a crucial structural element of biological membranes and a precursor to steroid hormones) are all examples of steroid hormones.

Water-soluble ligands

Water-soluble ligands are polar so they cannot pass through the plasma membrane on their own. There are also water-soluble ligands that are too large to enter the membrane at all. As such, most water-soluble ligands bind to cell-surface receptors on the plasma membrane where extracellular signals are turned into intracellular signals. This group of ligands includes peptides and proteins.

Types of cell receptors

There are two types of cell receptors: internal and cell-surface receptors. We will also go into the three main categories of cell-surface receptors.

Internal receptors

Internal receptors--also known as cytoplasmic or intracellular receptors--can be found in the cytoplasm. They typically interact with hydrophobic ligand molecules that move across the plasma membrane. Upon entering the cell, these hydrophobic molecules bind to proteins that regulate transcription as part of gene expression.

Gene expression refers to the biological process in which information in the DNA of a cell is transformed into a sequence of amino acids which becomes a protein. Gene expression takes place in two steps: transcription and translation.

Transcription refers to the process by which information in DNA is copied into an mRNA (messenger RNA) molecule

The binding of the ligand to the internal receptor triggers a conformational change in which a DNA-binding site is exposed on the protein. The complex consisting of the ligand and the receptor moves into the nucleus and binds to certain regions of chromosomal DNA, leading to the initiation of transcription.

Internal receptors do not need to pass signals onto other receptors or messengers in order to influence gene expression.

Cell surface receptors

Cell surface receptors span the plasma membrane, meaning each receptor has extracellular (outside the cell), transmembrane (in the interior of the cell membrane), and cytoplasmic or intracellular (in the cytoplasm) domains.

Unlike internal receptors, cell-surface receptors need to convert extracellular signals into intracellular signals in a process called signal transduction. Ligands that bind with cell-surface receptors are not required to enter the cell.

Cell-surface receptors can be classified into three major categories based on the mechanism by which they reconfigure extracellular signals into intracellular ones: G-Protein-coupled receptors, ion channel receptors, and enzyme-linked receptors.

Ion channel receptors

Ion channel-linked protein receptors work by binding a ligand and then opening a channel across the plasma membrane that allows specific ions to pass through (Fig. 1).

This type of cell surface receptor has a wide membrane-spanning region in which a channel can be constructed. Many amino acids in the transmembrane region are hydrophobic, so they are able to interact with the phospholipid fatty acid tails which constitute the core of the plasma membrane.

On the other hand, amino acids lining the inside of the ion channel are hydrophilic, so they can allow water or ions to pass through. When a ligand attaches to the extracellular region of the channel, the proteins undergo shape change to accommodate the entry of ions like sodium, calcium, and hydrogen.

One example of ion channel receptors are those located on neurons. One such ion channel receptor is the ionotropic glutamate receptor, which binds the ligand glutamate. Glutamate is an excitatory neurotransmitter, that elicits activation of the neuron it binds to. When glutamate binds to ionotropic glutamate receptors, the pore opens and sodium is able to flow into the cell, causing the plasma membrane to become depolarized, which, when threshold is reached, triggers an action potential. As the action potential moves across the cell's surface, it can initiate other cellular processes.

Enzyme-linked receptors

Enzyme-linked receptors are found on the surface of the cell membrane. Some have an intracellular domain that interacts with enzymes, while others have an intracellular domain that is, in itself, an enzyme. Most enzyme-linked receptors have large extracellular and intracellular domains, with the region spanning the membrane consisting of a single alpha-helical region of a peptide strand.

When a ligand binds to the extracellular region, a signal is sent through the membrane, which activates the enzyme. The activated enzyme triggers a series of reactions that leads to a cellular response.

Enzyme-linked receptors allow signaling molecules to influence cell function without actually entering the cell since they interact with both extracellular signals and molecules present inside the cell. This is crucial as the majority of signaling molecules are either charged or too large to pass through the plasma membrane.

G Protein coupled receptors

G protein coupled receptors work by binding a ligand and then activating a type of membrane protein known as a G protein, which then interacts with an ion channel or an enzyme in the plasma membrane. G proteins are made up of several subunits:

  • The alpha subunit (Gα) binds and hydrolyzes Guanosine triphosphate (GTP)

  • The beta and gamma subunits (Gβγ) inhibit Gα and take part in signaling reactions

G protein coupled receptors span the membrane 7 times and contain a guanine nucleotide exchange (GEF) domain.

As such, when G protein coupled receptors bind ligands, the GEF domain catalyzes Gα to bind GTP. Gα-GTP dissociates from the Gβγ, and then some Gα subunits stimulate the activities of subsequent enzymes in the series, while others inhibit them (Fig. 2).

Example of signal reception in biology

An example of an enzyme-linked receptor is the tyrosine kinase receptor (Fig. 3). A protein kinase adds phosphate groups from ATP to a protein molecule. The tyrosine kinase receptor transfers phosphate groups specifically to tyrosine residues.

When the signal molecules bind to the extracellular region of two adjacent tyrosine kinase receptors, the two receptors undergo dimerization. Then, the tyrosine residues on the intracellular domain of the receptors undergo phosphorylation, enabling them to transmit the signal to the next messenger within the cytoplasm.

An example of receptor tyrosine kinase is HER2. HER2 is permanently active in 30% of human breast tumors, which leads to uncontrolled cell division. HER2 receptor tyrosine kinase autophosphorylation is inhibited by lapatinib, a medication used to treat breast cancer, which slows tumor development by 50%.

Dimerization refers to the process by which two identical molecules are attached via a chemical bond

Phosphorylation refers to the addition of a phosphate group to a molecule

Autophosphorylation refers to the the process by which the receptor attaches phosphates onto itself

Signal Reception - Key takeaways

  • Cell signaling has three basic steps: signal reception, signal transduction, and cellular response.
  • Signal reception is the stage in which the ligand binds to a receptor protein in or on the surface of the plasma membrane.
  • There are two types of receptors: internal and cell surface receptors.
    • Internal receptors do not need to pass signals onto other receptors or messengers.
    • Cell surface receptors reconfigure extracellular signals into intracellular ones through signal transduction.

References

  1. “Intro to Chemical Signaling and Communication by Microbes.” Organismal Biology, https://organismalbio.biosci.gatech.edu/chemical-and-electrical-signals/intro-to-chemical-signaling-and-signal-transduction/. Accessed 30 June 2022.
  2. Cell Biology@Yale. medcell.med.yale.edu, http://medcell.med.yale.edu/lectures/cell_communication.php. Accessed 30 June 2022.
  3. “Cell Signaling | Learn Science at Scitable.” Cell Signaling | Learn Science at Scitable, www.nature.com, https://www.nature.com/scitable/topicpage/cell-signaling-14047077/. Accessed 30 June 2022.
  4. OpenStaxCollege. “Signaling Molecules and Cellular Receptors – Biology.” Signaling Molecules and Cellular Receptors – Biology, pressbooks-dev.oer.hawaii.edu, http://pressbooks-dev.oer.hawaii.edu/biology/chapter/signaling-molecules-and-cellular-receptors/. Accessed 30 June 2022.

Frequently Asked Questions about Signal Reception

There are three types of receptors involved in signal reception: G Protein-coupled receptors, ion channel receptors, and enzyme-linked receptors.

In the reception phase of cell signaling, the ligand binds to a receptor protein in or on the surface of the plasma membrane.

The signal reception phase of cell signaling is important because this is when the signal--typically from the external environment--is detected by the cell. 

The 3 stages of cell signaling are signal reception, signal transduction, and cellular response. During signal reception, the signal is detected from the extracellular environment. During the signal transduction phase, the signal is transmitted toward the interior of the cell. Finally, during the cellular response phase, the signal reaches the target proteins involved in the cellular process. 

Reception in cell signaling works with the ligand binding to a receptor protein in or on the surface of the plasma membrane. 

Final Signal Reception Quiz

Question

What does it mean when we say that ligands and receptors exhibit specificity? Cite an example. 

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Answer

Both ligands and receptors have a high level of specificity: typically, a ligand binds to a specific receptor. For example, growth factor receptors bind growth factors, and dopamine receptors bind dopamine.

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Question

Where are internal receptors found?

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Answer

Cytoplasm

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Question

What are the three major categories of cell-surface receptors?

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Answer

Ion channel-linked receptors

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Question

Explain how ion channel receptors work.

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Answer

Ion channel protein receptors work by binding a ligand and then opening a channel across the plasma membrane. When a ligand attaches to the extracellular region of the channel, the proteins undergo shape change to accommodate the entry of ions like sodium, calcium, and hydrogen. 

Show question

Question

Where are enzyme-linked protein receptors found?

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Answer

Cell surface

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Question

How do enzyme-linked receptors interact with enzymes?

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Answer

Some have an intracellular domain that interacts with enzymes while others have an intracellular domain that is, in itself, an enzyme.

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Question

What is the difference between internal and cell surface receptors?

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Answer

Internal receptors are found in the cytoplasm, while cell surface receptors span the plasma membrane. 

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What is a G protein coupled receptor?

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Answer

G protein coupled receptors work by binding a ligand and then activating a type of membrane protein known as G protein, which then interacts with an ion channel or an enzyme in the plasma membrane. 

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Question

Internal receptors typically interact with what type of molecules?

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Answer

Hydrophobic

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Question

Explain how a G protein coupled receptor works.


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Answer

When G protein coupled receptors bind ligands, the GEF domain catalyzes Gα to bind GTP. Gα-GTP dissociates from the Gβγ, some Gα subunits stimulate the activities of subsequent enzymes in the series, while others inhibit them

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Question

In cell signaling, molecules that deliver signals are called ____.

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Answer

Ligands

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Receptors are usually what kind of biological molecule?

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Proteins

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Where do signals come from?

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From cells in other parts of the organism

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What is autophosphorylation?

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Autophosphorylation refers to the the process by which the receptor attaches phosphates onto itself.

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Question

What happens when ligands bind to the extracellular region of two adjacent tyrosine kinase receptors?


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Answer

The tyrosine kinase receptors dimerize. 

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Ligands are also known as

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Signaling molecules

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When a ligand binds to a receptor, a signal travels across the membrane and into the cytoplasm; the continuation of a signal in this manner is known as __.

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Signal transduction

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Ligands that bind with __ are not required to enter the cell.

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Answer

Cell-surface receptors

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What type of ligands diffuse through the plasma membrane and bind to internal receptors?

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Answer

Hydrophobic ligands

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What type of ligands cannot diffuse through the plasma membrane and have to undergo signal transduction?

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Answer

Hydrophilic ligands

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Which of the following are hydrophilic ligands?

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Answer

Peptides

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Which of the following ligands can diffuse through through the plasma membrane?

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Answer

Testosterone

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Describe how hormones travel in endocrine signaling.

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Hormones are signaling molecules that are produced in one part of the body and are able to create biological changes in other parts of the body, even at a distance. Hormones travel through the bloodstream, which dilutes them in the process. As such, whereas paracrine signals can be present in high concentrations, hormones tend to be present in small amounts when they act on their target cells.

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Ligands that are involved in the transmission of signals between nerve cells are called __.

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Neurotransmitters

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Compare endocrine and paracrine signals.

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Paracrine signals are transmitted to nearby cells, whereas endocrine signals are transmitted to distant cells within the same body. 

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What happens when a water-soluble ligand binds to a receptor?

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Answer

The extracellular signal is converted to an intracellular signal.

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During autocrine signaling, where do ligands come from?

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Within the same cell

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How are responses localized during paracrine signaling?

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Paracrine ligand molecules tend to be promptly broken down by enzymes or eliminated by nearby cells so that the response is kept localized.

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Hormones are ____.

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Polar

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What kind of molecules can pass through cell junctions?

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Answer

Although large molecules like proteins and DNA cannot fit through the channels, small molecules like calcium ions (Ca2+) can.

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Enzyme-linked receptors are what type of receptors?

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Cell-surface receptors

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What are enzyme-linked receptors?

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Enzyme-linked receptors are cell-surface receptors that work by binding a ligand, which sends a signal through the membrane and activating the enzyme, triggering a series of reactions, eventually leading to a response.

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Describe the enzymatic activity of an enzyme-linked receptor.

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The cytosolic domain of the enzyme-linked receptor contains either intrinsic enzyme activity or directly interacts with an enzyme.

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Where is the ligand-binding site of the enzyme-linked receptor found?

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Extracellular domain

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What domain in the enzyme-linked receptor activates the signaling pathway?


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Intracellular domain

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Which of the following are types of enzyme-linked receptors?

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Histidine-kinase-associated receptors

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Receptor tyrosine kinases (RTK) ___ tyrosine residues on intracellular signaling proteins. 

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Answer

Phosphorylate

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Receptor-like tyrosine phosphatases ___ phosphate groups from tyrosine residues in specific intracellular signaling proteins.

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Answer

Remove

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Question

Describe how histidine-kinase-associated receptors activate the signaling pathway.

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Answer

Histidine-kinase-associated receptors initiate a "two-component" signaling pathway in which the kinase phosphorylates itself on histidine and then passes the phosphate to a second intracellular signaling protein.

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Question

Receptor guanylyl cyclases generate second messenger ____  in the cytosol.

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Answer

Cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP)

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Question

How do enzyme-linked proteins activate the signaling pathway?

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Answer

For most enzyme-linked receptors, ligand binding induces their dimerization or, in some cases, oligomerization. This causes cytoplasmic enzymatic domains to combine, resulting in a change in enzymatic activity, which is essentially their activation. 

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Which types of enzyme-linked receptors tend to form heterodimers?

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Answer

Receptor serine–threonine kinases

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Question

​Explain how autophosphorylation occurs in receptor tyrosine kinases.


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Answer

When a ligand binds to the ligand-binding domain on the cell's surface, it activates the intracellular tyrosine kinase domain. Upon activation, the kinase domain moves a phosphate group from ATP to specific tyrosine side chains on receptor proteins as well as intracellular signaling proteins that interact with the phosphorylated receptors.

 

The rearrangement in receptor tyrosine kinases allows adjacent kinase domains of the receptor chains to cross-phosphorylate each other on numerous tyrosines, a process known as autophosphorylation.

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Question

How are insulin receptors different from other typical receptor tyrosine kinases?

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Answer

Whereas other RTKs form dimers upon ligand-binding, insulin receptors are tetramers to begin with. 

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How does the autophosphorylation of RTKs result in activation?

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Answer

Autophosphorylation of receptor tyrosine kinase cytosolic tails results in activation in two ways:

 

  1. The phosphorylation of tyrosines inside the kinase domain boosts the enzyme's kinase activity. 

  2. The phosphorylation of tyrosines outside the kinase domain generates high-affinity docking sites in the target cell for the binding of various intracellular signaling proteins.

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What are ion channels?

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Answer

Ion channels are channel proteins embedded in the plasma membrane. These ion channels facilitate the movement of ions across the membrane by acting as gated channels that open and close in response to certain stimuli. 

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Ion channel receptors are __.

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Answer

Cell-surface receptors

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Ion channel receptors are found in the __.

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Answer

Plasma membrane

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What are ion channel receptors?

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Answer

Ion channel-linked receptors are a type of cell-surface receptor that, upon binding a ligand, change shape such that a channel is formed across the plasma membrane, allowing specific ions to pass through. 

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Question

Amino acids that line the interior of the channel tend to be _____, so water or ions are able to pass through. 


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Answer

Polar

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