Enzyme-coupled receptors are transmembrane proteins with extracellular ligand-binding domains. Their intracellular domains possess intrinsic enzyme activity or interact with enzymes. enzyme-coupled receptors usually have a 1 transmembrane segment per subunit. Enzyme-coupled receptors, particularly receptor tyrosine kinases (RTKs). Humans possess around 60 RTKs, categorized into 20 structural subfamilies, each specific to its corresponding family of protein ligands. Inactive RTKs typically exist as monomers with inactive kinase domains in the absence of extracellular signals. ligand binding triggers RTK dimerization,bringing 2 cytoplasmic kinase domains activating their kinase domains. Ligand binding on extracellular side activates the RTK's kinase domain on the cytosolic side, leading to tyrosine phosphorylation. These phosphotyrosines serve as docking sites for intracellular signaling proteins, relaying the signal.

are transmembrane proteins with extracellular ligand-binding domains and intrinsic enzyme activity or interactions with enzymes in their intracellular domains.

1 transmembrane segment per subunit

type of enzyme-coupled receptor.

Humans possess around 60 RTKs, categorized into 20 structural subfamilies, each specific to its corresponding family of protein ligands.

Inactive RTKs typically exist as monomers with inactive kinase domains.

ligand binding,bringing 2 cytoplasmic kinase domains activating their kinase domains.

Ligand binding on extracellular side activates the RTK's kinase domain on the cytosolic side, leading to tyrosine phosphorylation.

serve as docking sites for intracellular signaling proteins, relaying the signal.

Intracellular signaling proteins that bind to phosphotyrosines often contain SH2 (binds phosphotyrosine) or SH3 (binds proline-rich motifs) domains.

SH2 (binds phosphotyrosine) or SH3 (binds proline-rich motifs) domains.

monomeric GTPases, part of the Ras superfamily

relay signals from cell-surface receptors and act as signaling hubs, interacting with various intracellular proteins to coordinate signal promotion along multiple downstream pathways.

One or more covalently Lipid attached groups anchor Ras to cytoplasmic membrane, enabling it to relay signals within the cell.

activate Ras by promoting GDP dissociation and GTP binding

inactivate Ras by stimulating GTP hydrolysis.

The Ras and Rho families of monomeric GTPases, part of the Ras superfamily, relay signals from cell-surface receptors. These GTPases act as signaling hubs, interacting with various intracellular proteins to coordinate signal promotion along multiple downstream pathways. One or more covalently Lipid attached groups anchor Ras to cytoplasmic membrane, enabling it to relay signals within the cell. * Ras-GEFs activate Ras by promoting GDP dissociation and GTP binding. * Ras-GAPs inactivate Ras by stimulating GTP hydrolysis.

The Ras and Rho families of monomeric GTPases, part of the Ras superfamily, relay signals from cell-surface receptors. These GTPases act as signaling hubs, interacting with various intracellular proteins to coordinate signal promotion along multiple downstream pathways. One or more covalently Lipid attached groups anchor Ras to cytoplasmic membrane, enabling it to relay signals within the cell. * Ras-GEFs activate Ras by promoting GDP dissociation and GTP binding. * Ras-GAPs inactivate Ras by stimulating GTP hydrolysis.

Short-lived RTK activation must be converted into longer-lasting signals to drive cellular proliferation or differentiation, ultimately altering gene expression. The Ras-MAP kinase pathway involves a cascade of three kinases: * Raf (MAPKKK): Activated by Ras, it phosphorylates and activates MEK. * MEK (MAPKK): Phosphorylates and activates ERK. * ERK (MAPK): The final kinase in the cascade. This sequential phosphorylation amplifies the initial signal. MAP kinase activates downstream targets by phosphorylation. This includes transcription factors and other kinases.

To drive cellular proliferation or differentiation, ultimately altering gene expression

Raf (MAPKKK) MEK (MAPKK) ERK (MAPK).

Raf is activated by Ras and phosphorylates and activates MEK.

MEK phosphorylates and activates ERK.

final kinase in the Ras-MAP kinase cascade

By phosphorylation, including transcription factors and other kinases.

Rho monomeric GTPases regulate both actin and microtubule cytoskeletons, controlling cell shape, polarity, motility, and adhesion also regulate cell-cycle progression, gene transcription, and membrane transport. plays a role in guidance of cell migration and nerve axon outgrowth, mediating cytoskeletal responses to activation of a special class of guidance receptors. Rho, Rac, and Cdc42 are key Rho GTPases, each with distinct downstream targets.

Actin and microtubule cytoskeletons

Cell shape, polarity, motility, and adhesion

Cell-cycle progression, gene transcription, and membrane transport

Guidance of cell migration and nerve axon outgrowth

Rho, Rac, and Cdc42

Rho GTPases with distinct downstream targets.

PI 3-kinase primarily phosphorylates inositol phospholipids, activated by both RTKs and GPCRs. It plays a crucial role in cell survival and growth. Phosphatidylinositol (PI) is a unique membrane lipid that can be reversibly phosphorylated at multiple sites on its inositol head group to create phosphoinositides PI(3,4,5)P3 is a docking site for signaling proteins, enabling formation of signaling complexes at plasma membrane, facilitating intracellular signal transduction. PI 3-kinase activation generates PI(3,4,5)P3, which recruits Akt and PDK1 to the plasma membrane via their PH domains, leading to Akt activation. Activated Akt phosphorylates targets at plasma membrane,cytosol,nucleus.

Inositol phospholipids

Both RTKs and GPCRs

Cell survival and growth

membrane lipid that can be reversibly phosphorylated at multiple sites on its inositol head group to create phosphoinositides

docking site for signaling proteins, enabling formation of signaling complexes at plasma membrane, facilitating intracellular signal transduction.

PI(3,4,5)P3, which recruits Akt and PDK1 to the plasma membrane via their PH domains, leading to Akt activation.

Phosphorylation of targets at the plasma membrane, cytosol, and nucleus.

• GPCR triggered: PKA • RTK triggered: MAP kinase Akt kinase • Triggered by both CaM kinase PKC

PKA

MAP kinase Akt kinase