Lecture 12: cell communicaion II Flashcards
Cell surface receptors:
1. G protein- coupled receptors
Associate with G proteins: bind GTP and GDP in the cytoplasm
G proteins bound to GDP: Inactive
G proteins bound to GTP: Active
Ligand binding to the receptor activates the G protein by replacing GDP with GTP
Cell surface receptors:
1. G protein activation
• G proteins are composed of α, β, and γ subunits. • α subunit: binds either GDP or GTP • When α is bound to GDP: α, β, and γ associate and the G protein is inactive • When the G protein is bound by an activated receptor: GDP is replaced by GTP and the α subunit separates from β and γ • α-GTP binds activates target proteins in the cell
Adrenaline Signaling in Heart Muscle
Activated protein kinase A phosphorylates proteins in the heart muscle, causing heart rate to increase.
Amplification of adrenaline signaling
- Activated receptors activate multiple G proteins. Which activates adenylyl cyclase enzymes
- adenylyl collapse enzymes produce cAMP. Activates protein kinase A.
- protein kinase A phosphorylates and activates proteins.
Termination of adrenaline signaling.
- phosphatases remove phosphate groups from proteins. Makes them inactive.
- GTP to GDP
- cAMP to AMP
Receptor kinases?
• Activated Receptor Kinases phosphorylate proteins in the cell
The MAP Kinase Pathway and Wound Healing.
- PDGF: released by platelet cells in response to a wound
- PDGF activates PDGF receptor kinases at the site of the wound
- Activated receptors activate Ras (Ras-GDP à Ras-GTP)
- Ras-GTP triggers a series of kinase activations that reaches the nucleus
- Activated kinases in the nucleus phosphorylate proteins that regulate the transcription of genes required for cell division and wound healing
Termination of RAS signaling.
• Phosphatases inactivate the receptor kinases and other kinases in the pathway
- Ras-GTP converts to Ras-GDP rendering it inactive; an active -
- Receptor Kinase is required to re- activate Ras
- Dissociation of PDGF from its receptor
Ligand gated ion channels.
• Signaling molecule binds to a channel protein
• The channel undergoes a conformational change that opens
it and allows ions to flow into or out of the cell
• The channel remains open as long as the signaling molecule remains
bound
Acetylcholine Receptors and Muscle Contractions
Acetylcholine binding opens ion channels allowing Na+ to flow into muscle cell.
Cell signaling problems that chase cancer.
• Increased Receptors: increased binding to signaling molecules that can lead to abnormal gene express/excess cell division
• Overproduction/Altered signaling molecule: cancer cells can overproduce or make altered forms of a signaling molecule that can lead to increased binding to receptors and abnormal cell responses
• Ras Mutations: associated with 30% of all human cancers: Ras-GTP does not convert to Ras-GDP and is always active