Signal Transduction by Second Messengers
and Protein Kinases
Organisms utilize phosphoinositide (PI) and
Ca2+ signaling pathways to control a diverse array of functions,
ranging from fertilization and development to vision and synaptic
plasticity. Defects in PI and Ca2+ signaling are implicated in
the pathogenesis of a wide range of diseases including birth
defects, mental illness, and cancer. Measurements on single cells
have revealed a complex spatiotemporal pattern of Ca2+ signaling.
Nearly all activated eukaryotic cells exhibit repetitive spikes
in their intracellular Ca2+ concentration, suggesting that this
process is fundamentally important in signal transduction. There
is evidence thatsimilarly complex spatial or temporal patterns
might occur for other second messengers such as diacylglycerol(DAG), inositol 1,4,5-trisphosphate (IP3), and
cAMP. The ultimate goal of the research is to understand how
these complex patterns of second messengers are generated, and
how they regulate cellular processes such as gene transcriptionS
motility, and metabolism. Current research focuses on: 1)
understanding how Ca2+ spikes and waves are generated by IP3 and
other second messengers, 2) determining how nuclear
concentrations of Ca2+, IP3 and DAG are regulated and
consequently control nuclear functions, and 3) deciphering how
Ca2+ spikes regulate the activity of kinases and phosphatases and
ultimately cellular activities. To address these questions, novel
techniques are being developed to measure the concentrations of
second messengers, and the level of substrate phosphorylation in
single cells.
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