L1: cell communication 1

what are the 3 characteristics of a signal

• speed

• duration

• mechanism

state the types of cell to cell signalling

• contact dependent

• synaptic

• paracrine

• endocrine

• pheremones

describe a type of contact-dependent signalling

notch pathway signalling for drosophila photoreceptors in eye disc morphogenetic furrow

describe a type of paracrine signalling

Hh and Dpp are large proteins with post-translational modifications which are secreted and interact with ECM components before moving to activate downstream signalling in local cells

describe a type of endocrine signalling

adrenaline produced by the adrenal glands acts via adrenergic receptors to produce a wide range of physiological responses including fight or flight

describe pheromone signalling

pheromones produced by queen bees send signalling controlling hives of tens of thousands of workers

how can cells respond to signalling

• altered metabolism

• altered gene expression

• altered cell shape/movement

how is signalling regulated

cells can react differently on the basis of the strength of the signal they receive - e.g. morphogen gradients where responses occur at specific thresholds

describe an example of morphogen signalling

during drosophila development Bicoid mRNA is deposited by the mother in the anterior of the egg + forms a gradient defining the anterior parts of the resulting embryo

what determines the speed of cell responses to signalling

what is altered within the cell:

changing the structure of an existing protein is very fast

changes post translation modifications is quite fast

changing protein levels via gene expression is relitively slow

why is signalling regulation important

issues with regulation can lead to cancers (both caused by issues with kinases):

myeloproliferative neoplasms (mutation in negative regulatory ‘pseudokinase’ domain of JAk2 associated with >95% of polycythaemia vera blood cancer patients)

chronic myeloid leukaemia (BCR-Abl fusion protein causes sustained Abl tyrosine kinase expression by Bcr promotor, leads to CML)

at which stages can a signalling pathway be regulated

extracellular ligand/receptor

intracellular transduction of signal

effectors feedback onto their own pathways

describe a positive feedback loop

notch pathway lateral inhibition - system ‘maxes’ out and is sustained beyond stimulus

describe a negative feedback loop

JAK/STAT pathwaya downregulated by SOCS negative regulator - system ‘maxes’ out only while stimulus is present and decays after stimulus

how is signalling regulated by phosphorylation

signal activates protein kinase to phosphorylate + turn on protein. protein phosphotase then removes phosphate to switch protein off

how is signalling regulated by GTP-binding

GDP bound to protein switched with GTP to switch protein on by exchange factor (GEF), small GTPase (GAP) hydrolyses GTP→GDP to switch protein off

what are the 2 major groups of protein kinases in eukaryotes

serine/threonine kinases + tyrosine kinases