Lecture 15- Cell Signaling I Flashcards
differential gene expression theory
- genome is constant in all somatic cells
- only small proportion of genome in any cell type is expressed
- unused genes that are not transcribed are not mutated or destroyed, they retain potential to be expressed
how many protein coding genes in humans are devoted to cell signaling?
over 7,000 out of 21,000
general principles of signaling
- signaling cells send signaling molecule (ligand) that is detected by target cell
- receptors in target cells recognize and respond specifically to signal molecule (only cells that have a receptor for a signal can respond to that signal)
- triggers intracellular signaling pathway to effectors
ligands can be…
proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, gases
intracellular signaling pathway
relay, amplify, integrate, distribute
effectors
may alter gene expression, metabolism, cell shape or movement, etc.
signal transduction
process of translating an extracellular signal into intracellular effectors that alter cell behavior
signals have act over long or short range
ex. insulin (produced by beta cells in pancreas and regulates glucose uptake in cells all over body)
ex. hormones secreted by endocrine cells
neuron example of long/short range signals
- axon of neuron can be far away from neuronal cell body
- axon terminates at specialized junctions called synapses
- once activated, neuron sends electrical impulses along axon, leading to release of neurotransmitters (signals) at the nerve terminal
lateral inhibition example
mediated by membrane-bound ligand (delta) and membrane-bound receptor (notch)
information conveyed by signal depends on how target cells receives and interprets the signal (their developmental history and current state)
signals can be of different types
small/large molecules, light, mechanosensation
signals can act over long or short range
endocrine, paracrine (autocrine), synaptic, contact-dependent
same signal can induce different responses
depending on history and status of target cell
signals can act rapidly or slowly
changes of protein function or gene expression
receptors can be intracellular or on cell surface
- intracellular receptors: can accept small hydrophobic signal molecules that have passed through cell membrane, often in cytosol or nucleus, regulate gene transcription or other functions
- cell surface: binds to large hydrophilic molecules on outside of cell and then generate 1+ intracellular signaling molecules inside cell
steroid hormones regulate transcription
- each hormone binds a different receptor
- each receptor acts at different sites in DNA
- a given hormone usually regulates (activate or repress) different sets of genes in different cell types
cell surface receptors relay extracellular signals via intracellular signaling pathways
extracellular signal molecule -> receptor protein -> intracellular signaling molecules -> effector proteins -> target cell responses
intracellular signaling molecules
- adaptors, kinases, phosphatases, GTP binding proteins, proteases, other enzymes, lipids (PIP2)
- 2nd messengers: cGMP, cAMP, Ca++
effector proteins and target cell responses
- metabolic enzyme -> altered metabolism
- cytoskeletal protein -> altered cell shape or movement
- transcription regulator -> altered gene expression
functions of intracellular signaling pathways
primary transduction -> relay by adaptors -> transduce and amplify
-> integrate -> feedback (may integrate again) -> distribute -> target cell responses
many key intracellular signaling proteins act as molecular switches
a) signaling by protein phosphorylation: kinases (serine/threonine kinases, tyrosine kinases)
b) signaling by GTP-binding proteins: small GTPases (Ras, Ran, Rab, etc)
2nd messengers amplify and transduce the signal
- cGMP, cAMP, Ca++
- small intracellular messenger molecules
feedback regulation within an intracellular signaling pathway can adjust the cell’s response to a signal
a) signaling pathway 1: positive feedback -> all or none response
b) signaling pathway 2: negative feedback -> response that oscillates on or off