Receptor Tyrosine Kinases

RTK structure

Receptor Tyrosine Kinase (RTK) structure includes transmembrane proteins with ligand binding domains on the outer surface of the plasma membrane (PM) and cytosolic domains that associate with trimeric G proteins.

GPCRs

G Protein-Coupled Receptors (GPCRs) are transmembrane proteins with ligand binding domains on the outer surface of the PM and associate with trimeric G proteins, having seven transmembrane segments.

Activation of RTKs

The activation of RTKs involves binding of signal proteins to the ligand-binding domain on the extracellular side of the receptor, leading to phosphorylation of tyrosine side chains on the cytosolic part, creating phosphotyrosine docking sites for intracellular signaling proteins.

Dimerization in RTK activation

Most RTKs dimerize upon ligand binding, bringing the two cytoplasmic kinase domains together, promoting their activation through trans-autophosphorylation or conformational changes.

Ras signaling

Ras, a GTPase, mediates signaling by most RTKs and can be activated by Ras guanine nucleotide exchange factors (Ras-GEFs) or inhibited by Ras GTPase activating proteins (Ras-GAPs).

PI3K signaling

RTKs can activate Phosphoinositide 3-Kinase (PI3K), which phosphorylates inositol phospholipids, promoting cell survival and growth by generating phosphoinositide docking sites and activating phospholipase C-γ.

Effector proteins of Ras

Activated Ras interacts with various families of effector proteins, leading to the activation of MAP kinase signaling modules and diverse downstream signaling pathways.

PH domains

Pleckstrin Homology (PH) domains are protein-protein interaction domains that bind to PIP3, facilitating the assembly of signaling complexes and increasing the specificity of binding in intracellular signaling pathways.