RESUMO
Calcium (Ca2+) is a versatile second messenger that regulates a wide range of cellular functions. Although it is not established how a single second messenger coordinates diverse effects within a cell, there is increasing evidence that the spatial patterns of Ca2+ signals may determine their specificity. Ca2+ signaling patterns can vary in different regions of the cell and Ca2+ signals in nuclear and cytoplasmic compartments have been reported to occur independently. No general paradigm has been established yet to explain whether, how, or when Ca2+ signals are initiated within the nucleus or their function. Here we highlight that receptor tyrosine kinases rapidly translocate to the nucleus. Ca2+ signals that are induced by growth factors result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. This novel signaling mechanism may be responsible for growth factor effects on cell proliferation.
Assuntos
Humanos , Proliferação de Células , Sinalização do Cálcio/fisiologia , Núcleo Celular/fisiologia , Receptores Proteína Tirosina Quinases/metabolismo , Núcleo Celular/enzimologiaRESUMO
Calcium (Ca2+) is a versatile second messenger that regulates a wide range of cellular functions. Although it is not established how a single second messenger coordinates diverse effects within a cell, there is increasing evidence that the spatial patterns of Ca2+ signals may determine their specificity. Ca2+ signaling patterns can vary in different regions of the cell and Ca2+ signals in nuclear and cytoplasmic compartments have been reported to occur independently. No general paradigm has been established yet to explain whether, how, or when Ca2+ signals are initiated within the nucleus or their function. Here we highlight that receptor tyrosine kinases rapidly translocate to the nucleus. Ca2+ signals that are induced by growth factors result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. This novel signaling mechanism may be responsible for growth factor effects on cell proliferation.
Assuntos
Sinalização do Cálcio/fisiologia , Núcleo Celular/fisiologia , Proliferação de Células , Receptores Proteína Tirosina Quinases/metabolismo , Núcleo Celular/enzimologia , HumanosRESUMO
Nuclear calcium (Ca(2+)) regulates a number of important cellular processes, including gene transcription, growth, and apoptosis. However, it is unclear whether Ca(2+) signaling is regulated differently in the nucleus and cytosol. To investigate this possibility, we examined subcellular mechanisms of Ca(2+) release in the HepG2 liver cell line. The type II isoform of the inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R) was expressed to a similar extent in the endoplasmic reticulum and nucleus, whereas the type III InsP(3)R was concentrated in the endoplasmic reticulum, and the type I isoform was not expressed. Ca(2+) signals induced by low InsP(3) concentrations started earlier or were larger in the nucleus than in the cytosol, indicating higher sensitivity of nuclear Ca(2+) stores for InsP(3). Nuclear InsP(3)R channels were active at lower InsP(3) concentrations than InsP(3)R from cytosol. Enriched expression of type II InsP(3)R in the nucleus results in greater sensitivity of the nucleus to InsP(3), thus providing a mechanism for independent regulation of Ca(2+)-dependent processes in this cellular compartment.