Biosignaling 3: Videos & Practice Problems

Phospholipase C (PLC) is an enzyme activated by G proteins in G protein-coupled receptor (GPCR) signaling. When a ligand binds to a GPCR, the G protein activates PLC. PLC then cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into two secondary messengers: inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 diffuses into the cytoplasm and binds to IP3 receptors on the endoplasmic reticulum, causing the release of calcium ions (Ca²⁺) into the cytoplasm. DAG remains in the membrane and, along with Ca²⁺, activates protein kinase C (PKC). This cascade of events leads to various cellular responses, such as changes in gene expression, metabolism, and cell growth.

The insulin receptor is a type of receptor tyrosine kinase (RTK) that functions by autophosphorylation. When insulin binds to the extracellular domain of the receptor, the receptor dimerizes and undergoes autophosphorylation at specific tyrosine residues. This phosphorylation activates the receptor's intrinsic kinase activity, leading to the phosphorylation of downstream signaling proteins such as insulin receptor substrate 1 (IRS1). IRS1 activates a cascade involving the RAS protein complex, MEK, and ERK, which ultimately leads to gene expression changes. Additionally, IRS1 activates protein kinase B (PKB), which increases glucose transporter (GLUT4) translocation to the cell membrane and promotes glycogen synthesis by inactivating glycogen synthase kinase 3 (GSK3).

Phospholipase C (PLC) produces two secondary messengers: inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 is water-soluble and diffuses through the cytoplasm to bind to IP3 receptors on the endoplasmic reticulum, triggering the release of calcium ions (Ca²⁺) into the cytoplasm. This increase in Ca²⁺ concentration can activate various calcium-dependent processes, including muscle contraction and enzyme activation. DAG remains in the plasma membrane and, together with Ca²⁺, activates protein kinase C (PKC). PKC phosphorylates target proteins, leading to diverse cellular responses such as changes in gene expression, cell growth, and metabolism.

Insulin signaling increases glucose uptake in cells through a series of steps involving the insulin receptor, a receptor tyrosine kinase (RTK). When insulin binds to its receptor, the receptor undergoes autophosphorylation and activates insulin receptor substrate 1 (IRS1). IRS1 then activates protein kinase B (PKB), also known as Akt. Activated PKB promotes the translocation of glucose transporter 4 (GLUT4) vesicles to the cell membrane. GLUT4 transporters facilitate the uptake of glucose from the bloodstream into the cell. Additionally, PKB inactivates glycogen synthase kinase 3 (GSK3), leading to the activation of glycogen synthase and promoting glycogen storage. These processes collectively lower blood glucose levels.

Protein kinase C (PKC) plays a crucial role in cell signaling by phosphorylating various target proteins, leading to diverse cellular responses. PKC is activated by diacylglycerol (DAG) and calcium ions (Ca²⁺), which are produced during the activation of phospholipase C (PLC) in G protein-coupled receptor (GPCR) signaling. Once activated, PKC phosphorylates specific serine and threonine residues on target proteins, modulating their activity. This can result in changes in gene expression, cell growth, differentiation, and metabolism. PKC is involved in various physiological processes, including immune responses, neuronal signaling, and regulation of cell cycle and apoptosis.