Cell signalling Flashcards
Describe the structure of membrane receptors
Cell-surface receptors are integral membrane proteins that span the plasma membrane.
What is the importance of signalling in controlling cell behaviour?
Cell signalling controls growth, cell differentiation and development, metabolism and apoptosis. It also allows cells to interact with their environment and neighbouring cells. Defective signalling often results in disease.
List the different types of signal that a cell may encounter
Autocrine: feed-forward mechanism where cell releases signal which binds on the surface of that cell.
Paracrine: local signalling where a transmitter released from one cell to another neighbourign cell
Endocrine: transmitter or signal released at distal sites which travel to target cells
Cell-cell: membrane bound signals on one cell bind receptors on the surface of an adjacent target cell.
What are the five different types of cell signalling receptor?
Intracellular receptors (transcription factors, enzymes)
Receptors that are ion channels
Receptors with intrinsic enzyme activity
Receptors linked to soluble protein kinases
Receptors coupled to targets via G-proteins
List the three common mechanisms cells use to change behaviour
Alter gene transcription
Alter enzyme activity
Alter ion balance across the membane
What is the advantage of a multiple component signalling pathway over a single component pathway?
Multiple component signalling pathways allow amplification and integration of signalling cascades, whereas single component systems are either off or on depending on the presence of the signal.
Describe the role of second messengers in signalling
Second messengers facilitate amplificaion of an extracellular signal.
Second messengers are small, metabolically unique molecules. The binding of a ligand to a receptor leads to a rapid change in concentration from high to low. These then activate target proteins which alter the behaviour of the cell.
Discuss the importance of Ca2+ as a second messenger
The concentration of free Ca2+ in the cytosol is kept very low (maintained by ATP pumps that transport Ca2+ out or into the ER). Following a signal induced release there can be a 100-fold increase in Ca2+ concentration. Ca2+ can bind to and activate a variety of target proteins.
Muscle: triggers contraction
Nerves and Endocrine cells: induces vesicle fusion and exocytosis
Binds calmodulin and other Ca2+-binding proteins causing a conformational change which allows binding to other target proteins.
Discuss transcription factors as intracellular recptors for steroid hormones`
Transcription factors are ligand-activated receptors that transduce signals by modifying gene transcription. Steroid hormone receptors are found in the cytoplasm in the absence of their ligand.
Sterioid hormones (e.g. oestrogen, cortisol, progesterone, aldosterone) enter the cell by diffusion through the plasma membrane and bind to their receptor. The transcription factor then becomes activated and translocates to the nucleus where it activates or suppresses gene transcription by binding to response elements in the DNA.
Name the types of ligand that can bind to intracellular receptors (4)
Transcription factors: steroid hormines, small lipophillic molecules
Enzymes: NO binding to guanylate cyclase
Describe the nitric oxide in vasodilation
Nitric oxide produced by endothelilal cells diffuses across the plasma membrane of smooth muscle cells and binds to guanylate cyclase. This converts GTP to cGMP which activates PKG. PKG phosphorylates MLCK, decreasing it’s activity and also promotes the uptake of Ca2+ into intracellular stores.
This causes muscle relaxation, dilating the blood vessel
Name 5 different types of Ga receptor and their respective actions
- Gas - adenylate cyclase (glucagon, ACTH)
- Gai - inhibits andenylate cyclase (PGE1, adenosine
- Gat: stimulates cGMP phosphodiesterase (rhodopsin)
- Gaq - stimulates PLC (vasopressein)
- Ga13 - activates ion channels (Na+/H+ exchange)
What are the five muscarinic Ach receptor subtypes?
M1, M3, M5 couple to Gq, stimulate PLC
M2 couples to Gi, opens K+ channel
M4 couples to Gi to inhibit AC
Describe the signalling pathway used by atrial natriuretic peptide
ANP is released by atrial muscle in response to stretch (high blood pressure). It binds to the GC-A receptor in kidney cells and other tissues. Guanylate cyclase converts GTP to cGMP, which activates a variety of target proteins including PKG.
PKG phosphorylated Na+ channels and reduces NA reabsorption, induces vasodilation of blood vessels and increases salt exretion and urine production. This reduces blood pressure
Describe the signalling pathway used by epidermal growth factor
The epidermal growth factor receptor is a type 1 RTK.
Binding of EDF induces formation of homodimers which activates the receptor tyrosine kinase in each monomer. The receptors undergo mutual phosphorylation of tyrosine residues.
pTyr provide binding sites for adaptor proteins via an SH2 domain. The adaptor proteins contain two SH3 domains which bind proline rich regions in a GEF. GEF activates Ras by exchanging GDP for GTP.
Active Ras initiates a map kinase cascade.