Biochemistry: Enzyme-Coupled Receptors

Transmembrane proteins that bind ligands on the outer surface of the plasma membrane. Their intracellular domains either act as enzymes or associate with enzymes.

The largest class of enzyme-coupled receptors. They have a cytoplasmic tyrosine kinase domain that phosphorylates specific tyrosine residues on intracellular proteins.

Causes receptor dimerization (coming together of two receptors). This activation step is usually followed by a cascade of intracellular signaling events.

A series of steps where activated RTKs recruit intracellular signaling proteins, activating signaling pathways that control cell behavior like growth and proliferation.

Activated RTKs can activate small GTPases like Ras. This is an important step in many signaling pathways.

Activated RTKs activate PI 3-kinase, which modifies lipids in the plasma membrane to create docking sites for signaling proteins.

The addition of a phosphate group to a molecule, frequently used as a way to regulate protein activity (e.g., kinase activity).

Three ways signaling proteins can link receptors: receptor dimerization after ligand binding; previously separate monomers brought together by a proteoglycan & clustered receptors on the membrane

A protein kinase that relays signals from cell surface receptors to the nucleus.

Phosphorylates downstream target proteins, including other kinases and gene regulatory proteins, affecting gene expression and cell behaviors, like proliferation & differentiation

Triggers downstream MAP kinase activation after binding to Sos.

GEF protein that promotes GTP exchange on Ras, crucial for activating the MAPK pathway.

Adaptor protein bound to receptor phosphotyrosine residues.

A group of intracellular switch proteins, including Ras and G-alpha subunits.

Monomeric GTPase switch protein that activates MAP kinase pathway without directly binding to receptors.

Growth factors, such as IGF (insulin-like growth factor), bind to RTKs, triggering their activation. This results in the recruitment and activation of the PI-3 kinase pathway.

PI-3 kinase is an enzyme that phosphorylates inositol phospholipids in the plasma membrane. These phosphorylated lipids act as docking sites for signaling proteins.

Signaling proteins, attracted by the phosphorylated lipids, relocate from the cytosol to the plasma membrane where they interact with each other and activate downstream pathways.

Akt is a protein kinase activated by the PI-3-kinase pathway. It plays a crucial role in promoting cell survival and growth.

Akt promotes cell survival by inhibiting programmed cell death (apoptosis) and by stimulating cell growth and proliferation.

While both RTKs and GPCRs can activate the PLC/IP3/DAG pathway, they use different isoforms of PLC. RTKs activate PLCγ, whereas GPCRs activate PLCβ.

SH2 domains are specific protein domains that bind to phosphorylated tyrosine residues. They are found in various signaling proteins, including PLCγ.

Phosphorylated lipids act as docking sites for signaling proteins, facilitating their relocalization to the plasma membrane. This clustering allows for efficient activation and interaction between signaling proteins.

A crucial signaling pathway involving PI 3-kinase and Akt, a serine/threonine kinase, that promotes cell survival and growth.

Akt, a serine/threonine kinase, often inactivates signaling proteins by phosphorylation, generally promoting cell survival and growth.

Akt directly phosphorylates and inactivates Bad, a protein involved in apoptosis, ultimately preventing cell death.

PI3K acts on lipids in the plasma membrane, creating docking sites for Akt. Activated Akt is then transported to the cytosol where it phosphorylates target proteins, affecting cell survival and growth.

Insulin stimulation in muscle and fat cells activates the PI3K-Akt pathway, promoting glucose uptake and glycogen synthesis, thus lowering blood glucose levels.

PDK1 and PDK2 are kinases that phosphorylate and activate Akt at the membrane, a key step in the PI3K-Akt signaling cascade.

PTEN is a phosphatase that terminates the PI3K-Akt pathway by removing phosphates from phosphoinositides, effectively shutting down the signal.

PTEN is often inactive in advanced cancers, leading to persistent PI3K-Akt pathway activation and uncontrolled cell growth.

Cytokines, signaling proteins, attach to their specific receptors on the cell surface.

Cytokine binding causes receptor subunits to pair up, forming a dimer. This is like two hands clasping together.

Activated JAKs add phosphate groups to the receptor, creating docking sites for STAT proteins. This is like attaching a magnet to pull in STATs.

Activated STATs pair up (dimerize) and travel into the nucleus. Think of a team carrying information to the boss.

STAT dimers bind to specific DNA sequences, controlling the expression of target genes. This is like a chef reading a recipe to make a specific dish.

A series of molecular events triggered by cytokines, leading to the regulation of gene expression. Think of a chain reaction starting with cytokine binding and ending with gene control.

Activated Ras triggers a signaling cascade involving a series of protein kinases, culminating in the activation of MAP kinases. These kinases phosphorylate transcription factors, influencing gene expression.

This pathway, involving receptor tyrosine kinases (RTKs), Ras, and MAP kinases, controls crucial cellular processes like cell division, differentiation, and metabolism.

Mutations in Ras that block GAP binding can lock Ras in its active state, causing uncontrolled cell growth and contributing to cancer development.

At high ligand concentrations, some cell-surface receptors (RTKs) are internalized by endocytosis, reducing the number of receptors on the cell surface. This makes cells less sensitive to the ligand.

Mutations in RTKs or proteins involved in the Ras/MAP kinase signaling pathway are frequently associated with cancer development.

Binding of a ligand to a receptor tyrosine kinase (RTK) triggers dimerization, where two receptors come together. This step is crucial for activating the RTK.