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31 Cards in this Set
- Front
- Back
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Types of intercellular signaling
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- Autocrine, cell to self
- Paracrine, messenger molecules travel short distances through intercellular space - Endocrine, messenger molecules reach their target cells through the bloodstream |
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Second messenger
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- Generated by effectors when cell surface receptors bind ligands
- Small substances which activate or inactivate specific proteins - Effect on these proteins causes changes in other receptors which recruit these proteins for messenging purposes |
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Effector
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- Enzyme which generates second messengers in combination with cell surface receptors
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Signal transduction
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- Occurs through series of proteins known as a signaling pathway
- Each protein alters the conformation of the next protein usually by phosphorylation Kinases add phosphate groups while phosphatases remove them - Target proteins are the ultimate recipients of the messenges |
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Protein phosphorylation
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- Addition of a phosphate group to a protein
- Can activate or inactivate and enzyme - Can increase or decrease interactions - Can change the subcellular location of the protein - Can trigger protein degradation |
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GPCRs
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- G protein-coupled receptors, the single largest superfamily of proteins encoded by animal genomes
- Have seven alpha-helical transmembrane domains and interact with G proteins |
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Ligands of GPCRs
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- Hormones, neurotransmitters, opium derivatives, chemoattractants (odourants, tastants), photons
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GPCR signal transduction
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- Ligand binding on exctracellular domain changes intracellular domain
- Affinity for G proteins increases, G protein is bound intracellularly - GDP is exchanged for GTP on the G protein, activating it - One ligand-bound receptor may activate multiple G proteins |
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GPCR second messengers
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- Phosphatidylinositol-specific phospholipase C-beta produces second messengers derived from phosphatidylinositol-inositol triphosphate (IP3) and diacylglycerol (DAG)
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DAG signal transduction
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- Diacylglycerol, GPCR second messenger
- Activates protein kinase C, which phosphorylates serine and threonine residues on target proteins - Phosphorylated phosphoinositides form lipid-binding domains called PH domains |
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Glucose metabolism
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- cAMP is synthesized from adenylyl cyclase
- cAMP evokes a reaction cascade that leads to glucose mobilization - cAMP diffuses into the cytoplasm and binds cAMP-dependent protein kinases (protein kinase A, PKA) |
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cAMP
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- Cyclic adenosine monophosphate, important second messenger in many biological processes, including glucose metabolism
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Arrestin
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- Phosphorylation of GPCRs allows binding of arrestins, which compete for binding with the G proteins
- Upon binding, GPCRs become desensitized - Arrestin-bound GPCRs must be recycled and returned to surface to be resensitized |
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Protein-tyrosine kinases
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- Enzymes which phosphorylate tyrosine residues on target proteins
- Over 90 different ones encoded by the human genome - Regulate cell growth, division, differentiation, survival, and migration |
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RTKs
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- Receptor protein-tyrosine kinases, cell surface receptors encoded by more than 60 genes in the human genome
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Receptor dimerization
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- Ligand binding causes protein kinase activity
- Tyrosine kinaase phosphorylates another subunit of the receptor (autophosphorylation) - RTKs phophorylate tyrosines within phosphotyrosine motifs |
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SH2 and PTB domain proteins
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- Include adaptor proteins that bind other proteins
- Include docking proteins which supply receptors with other tyrosine phophorylation sites - Includes signaling enzymes (kinases) which lead to changes in cell - Includes transcription factors |
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Ras-MAP kinase cascade
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- Cascade of enzymes resulting in activation of transcription factors
- MAP kinase (MAPK) is adapted to transmit different types of information - Scaffolding proteins tether signaling proteins in certain spatial orientations to increase interactions (e.g. AKAPs) - Scaffolds can cause conformational changes, can have enzymatic activity (e.g. yeast Pbs2), can prevent proteins from participating in other pathways |
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Signaling by the insulin receptor
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- Insulin receptor is a protein-tyrosine kinase
- Receptor autophosphorylates and associates with insulin receptor substrate proteins (IRSs) - IRSs bind proteins with SH2 domains to activate downstream signal molecules - SH2 domain proteins are kinases which phosphorylate lipids (e.g. Pl 3-kinase) - Terminal proteins of Pl3K activation include protein synthesis, glucose uptake, and glycogen synthesis |
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Glucose transport
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- PKB regulates glucose uptake by GLUT4 transporters
- GLUT4 transporters reside in intracellular membrane vesicles, which fuse to the membrane when insulin receptors bind ligands -Diabetes mellitus is causes by defects in insulin signaling, and Type 2 diabetes is causes by gradual insensitibity to insulin |
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Calcium as an intracellular messenger
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- Calcium levels are low in the cytosol because it is actively pumped out of the cell
- Calcium channels can be transiently opened by action potential (or calcium itself) - Calcium binds to calcium-binding proteins (such as calmodulin) |
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Signal convergence
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- Signals from unrelated receptors can converge to activate a common effector
- G protein-coupled receptors, receptor tyrosine kinases, and integrins can bind all lead to a docking site for Gbr2 |
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Signal divergence
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- Identical signals can diverge to activate a variety of effectors
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Signal crosstalk
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- Signals can be passed back and forth between pathways
- cAMP can block signals transmitted through the MAP kinase cascade - Ca(2+) and cAMP can influence each other's pathways |
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Apoptosis
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- An ordered process involving cell shrinkage, loss of adhesion, dissection of chromatin, and engulfment by phagocytosis
- Depends on the balance between pro- and anti- apoptotic signals - Activated by caspases |
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Caspases
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- Proteolytic enzymes involved in apoptotic changes
- Target protein kinases, lamins, cytoskeletal proteins, and caspase activated DNase (CAD) |
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Functions of apoptosis
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- Needed to form structure, organs, and tissues during embryonic development (e.g. spaces between digits)
- Active in adult humans, where 10-100 billion cells die every day - Apoptosis reduction or elevation linked to diseases such as cancer, Parkinson's, Alzheimer's, Huntington's, and Type I Diabetes |
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Extrinsic pathway of apoptosis
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- Tumour necrosis factor (TNF) is detected by a TNF cell surface receptor
- Bound TNF receptors recruit "procaspases" to the intracellular domain of the receptor - Procaspases convert other procaspases to caspases - Caspasses activate executioner caspases, leading to apoptosis |
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Intrinsic pathway of apoptosis
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- Proaptotic proteins stimulate mitochondria to leak proteins, mostly cytochrome C
- One in the cytosol, cytochrome C forms part of the apoptosome - This irreversibly commits the cell to apoptosis |
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Apoptosome
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- Multiprotein complex formed during intrinsic apoptosis
- Incluses cytochrome C and several molecules of procaspase-9 |
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Scramblase
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- Phospholipid enzyme which moves phosphatidylserine molecules to the outer leaflet of the plasma membrane
- Phosphatidylserine molecules are recognized a signal to other cells for phagocytosis |
