Name: cell-surface receptors and second messengers
Uploaded: 2023-04-30T11:39:37.000Z
Duration: 1 min 15 s
Channel: JoVE

Second messengers are low molecular weight non-protein molecules that relay signals to targets within the cell when ligands bind to receptors on the cell surface.
Second messengers include ions, such as calcium ions; cyclic nucleotides, such as cyclic AMP; and small molecules, such as phosphatidylinositol phosphate derivatives diacylglycerol or DAG and inositol trisphosphate or IP3.
Calcium ions are a widely occurring second messenger. The intracellular calcium concentration increases in response to specific signals and triggers diverse physiological functions. For example, in muscle cells, an increase in cytosolic calcium results in muscle contraction.
Different G-protein coupled receptor families activate enzymes that generate second messengers, including adenylyl cyclase which produces cyclic AMP and phospholipase C which produces DAG and IP3.
These second messengers can activate multiple downstream kinases, further amplifying the signal.

amplifying signals via second messengers

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces phospholipase C to hydrolyze the phospholipid, phosphatidylinositol biphosphate (PIP2), into two second messengers: diacylglycerol (DAG) and inositol triphosphate (IP3). DAG remains near the cell membrane and activates protein kinase C (PKC). IP3 translocates to the endoplasmic reticulum (ER) and becomes the opening ligand for calcium ion channels on the ER membrane, releasing calcium into the cytoplasm.
In the cAMP pathway, the activated receptor induces adenylate cyclase to produce multiple copies of cAMP from nearby adenosine triphosphate (ATP) molecules. cAMP can stimulate protein kinase A (PKA), open calcium ion channels, and activate the enzyme&#8211;&#160; Exchange-protein activated by cAMP (Epac).
Cyclic guanosine monophosphate (cGMP) is similar to cAMP. cGMP is synthesized from guanosine triphosphate (GTP) molecules when guanylyl cyclase is activated. As a second messenger, cGMP induces protein kinase G (PKG), which has many overlapping functions with PKA. However, PKG expression is restricted to vascular tissues, lungs, and the brain.
Phosphatidylinositol triphosphate (PIP3) is a second messenger derived from the phosphorylation of PIP2. This event is triggered when growth factors bind the receptor tyrosine kinase. PIP3 recruits Akt (aka. protein kinase B) to the membrane. This kinase is intimately involved in regulating cell survival pathways&#8211; including proliferation, apoptosis, and migration.

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed ...

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JoVE Core

Cell Biology

Unit 1

Principles of Cell Signaling

KEY TERMS AND CONCEPTS

cell-surface receptors and second messengers

Cell-surface receptors use second messengers to carry signals into the cell. Many receptor-binding ligands are hydrophilic, so they do not cross the cell membrane. Instead, they bind to receptors on the outside of the cell and pass the message to the cytoplasm.

G protein-coupled receptors can activate the phosphoinositol pathway and the cAMP pathway. In the phosphoinositol pathway, the receptor activates phospholipase C. This enzyme splits phosphatidylinositol biphosphate, or PIP2, into two second messengers: diacylglycerol, or DAG, and inositol triphosphate, or IP3.

DAG stays near the cell membrane and activates protein kinase C, or PKC. IP3 moves to the endoplasmic reticulum, or ER. There, it opens calcium ion channels on the ER membrane and releases calcium into the cytoplasm. This makes calcium part of the second messenger response.

In the cAMP pathway, the activated receptor stimulates adenylate cyclase. This enzyme makes many cAMP molecules from nearby adenosine triphosphate, or ATP. cAMP can activate protein kinase A, open calcium ion channels, and activate exchange-protein activated by cAMP, or Epac.

Cyclic guanosine monophosphate, or cGMP, works in a similar way to cAMP. It is made from guanosine triphosphate, or GTP, when guanylyl cyclase is activated. As a second messenger, cGMP activates protein kinase G, or PKG, which has many overlapping functions with PKA. PKG expression is restricted to vascular tissues, lungs, and the brain.

Phosphatidylinositol triphosphate, or PIP3, is another second messenger. It is formed when PIP2 is phosphorylated after growth factors bind to receptor tyrosine kinases. PIP3 recruits Akt, also called protein kinase B, to the membrane. Akt helps regulate cell survival pathways, including proliferation, apoptosis, and migration.

Cell-Surface Receptors and Second Messengers

cell-surface-receptors-and-second-messengers

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Cell-surface receptors use second messengers to carry signals into the cell. Many receptor-binding ligands are hydrophilic, so they do not cross the cell membrane. Instead, they bind to receptors on the outside of the cell and pass the message to the cytoplasm. G protein-coupled receptors can activate the phosphoinositol pathway and the cAMP pathway. In the phosphoinositol pathway, the receptor activates phospholipase C. This enzyme splits phosphatidylinositol biphosphate, or PIP2, into two...

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key terms and concepts

Explore how hydrophilic ligands signal through cell-surface receptors and second messengers like DAG, IP3, cAMP, cGMP, and PIP3 in high school biology.

Cell-Surface Receptors and Second Messengers | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Cell-Surface Receptors and Second Messengers

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