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ID 1020

Pathways, A bevy of interactions

Description:
In this section learn that receptors activate each other before binding an adaptor molecule and an exchange factor.
Transcript:
From our position in the cell's cytoplasm, we can see the ends of the receptor (in gray) being drawn together as the growth factor outside the cell binds. The receptor ends activate each other before binding an adaptor molecule (shown in pink) and an exchange factor (shown in light purple). An important protein in this pathway, known as Ras (shown in red) then swings around to be activated. Ras, in turn, activates three white "Raf" proteins, before another protein (shown in blue) moves in to deactivate it. Ras is a key "switch" in this pathway – mutations in the ras gene and protein are common in cancer cells. Molecules identified: Raf: A protein that interacts with the Ras protein. Raf is an example of a kinase enzyme, able to activate other proteins by adding phosphate molecules to serine and threonine amino acids. Mutations in the Raf protein are present in a large percentage of human malignant melanomas. Platelet derived growth factor (PDGF) receptors: PDGF receptors are large membrane-spanning proteins with an extracellular and an intracellular component. Two PDGF receptor proteins "dimerize" to bind a single platelet-derived growth factor. The cytoplasmic portion has kinase activity – able to add phosphate molecules to other molecules to activate them. This receptor can contribute to cancer if rendered active for an extended period of time. Growth factor receptor-bound protein 2 (Grb2): A protein that acts as adaptor molecule between a growth factor receptor and other signaling proteins. In a key signaling pathway, Grb2 binds an active PDGF receptor and activates a guanine-nucleotide exchange factor for the Ras protein. Ras: A protein loosely associated with the inner surface of the cell membrane. The Ras protein binds guanine nucleotides – guanosine diphosphate (GDP) and guanosine triphosphate (GTP). When a stimulatory signal arrives, Ras releases its GDP and acquires a GTP molecule, entering an active state and emitting a signal to another protein. After transmitting the signal, Ras deactivates itself by cleaving a phosphate molecule from the GTP to reduce it to GDP, or another protein called Ras-GAP comes in to break the GTP down. A single amino acid change can alter the function of Ras, causing it to bind GTP but making it unable to deactivate. Ras mutations are prevalent in many human cancers, including colon, skin, and lung. Ras guanine exchange factor (GEF): Activates the Ras protein by exchanging a bound guanosine diphosphate (GDP) for guanosine triphosphate (GTP). Platelet derived growth factor (PDGF) receptors: PDGF receptors are large membrane-spanning proteins with an extracellular and an intracellular component. Two PDGF receptor proteins "dimerize" to bind a single platelet-derived growth factor. The cytoplasmic portion has kinase activity – able to add phosphate molecules to other molecules to activate them. This receptor can contribute to cancer if rendered active for an extended period of time. Ras GTPase activating protein (GAP): A regulator of the Ras protein's signaling activity. Ras-GAP stimulates Ras's own weak ability to reduce bound guanosine triphosphate (GTP) to guanosine-diphosphate (GDP), thereby rendering itself inactive. See Ras.
Keywords:
ras protein, malignant melanomas, growth factor receptor, receptor proteins, cancer cells, guanosine triphosphate, pdgf receptor, amino acids, key switch, diphosphate, inner surface, gtp, cytoplasm, nucleotides, bevy, extracellular, receptors, raf
Creative Commons License This work by Cold Spring Harbor Laboratory is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

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