TY - JOUR
T1 - An expanded view of inositol signaling
AU - York, John D.
AU - Guo, Shuling
AU - Odom, Audrey R.
AU - Spiegelberg, Bryan D.
AU - Stolz, Leslie E.
N1 - Funding Information:
We wish to thank Dr. Susan R. Wente (Washington University, St. Louis, MO), without whom much of this work would have not been possible. Our collaboration has been a truly uplifting experience that we hope continues well into the new millennium. This work is supported by a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, the Howard Hughes Medical Institute, and the National Institutes of Health (HL-055672).
PY - 2001
Y1 - 2001
N2 - The long-range goal of our work is to elucidate how diverse extracellular stimuli elicit selective cellular responses through the activation of inositol polyphosphate (IP) signaling pathways. Defects in IP signaling pathways result in disease states such as Lowe syndrome, myotubular myopathy and cancer - through defects in the tumor suppressor PTEN. There are over 30 IP molecules, the majority of which have not been studied as messengers. It is our hypothesis that such IPs, designated as "orphans," may have important signaling roles. In support of this, we have recently defined novel roles for orphan IPs in regulating membrane trafficking, cytoskeletal organization, gene expression and mRNA export. These data indicate that cells are capable of producing multiple IP signals in response to stimulation. Thus, it seems plausible that individual agonists produce distinct patterns of IP signals, which thereby enable diverse cellular responses. Additionally, we have uncovered a family of lithium targets with relevance to manic depressive disease. An additional theme emerging from our work is that certain inositol signaling pathways are compartmentalized to the nucleus and directly effect nuclear function.
AB - The long-range goal of our work is to elucidate how diverse extracellular stimuli elicit selective cellular responses through the activation of inositol polyphosphate (IP) signaling pathways. Defects in IP signaling pathways result in disease states such as Lowe syndrome, myotubular myopathy and cancer - through defects in the tumor suppressor PTEN. There are over 30 IP molecules, the majority of which have not been studied as messengers. It is our hypothesis that such IPs, designated as "orphans," may have important signaling roles. In support of this, we have recently defined novel roles for orphan IPs in regulating membrane trafficking, cytoskeletal organization, gene expression and mRNA export. These data indicate that cells are capable of producing multiple IP signals in response to stimulation. Thus, it seems plausible that individual agonists produce distinct patterns of IP signals, which thereby enable diverse cellular responses. Additionally, we have uncovered a family of lithium targets with relevance to manic depressive disease. An additional theme emerging from our work is that certain inositol signaling pathways are compartmentalized to the nucleus and directly effect nuclear function.
UR - http://www.scopus.com/inward/record.url?scp=0034983856&partnerID=8YFLogxK
U2 - 10.1016/S0065-2571(00)00025-X
DO - 10.1016/S0065-2571(00)00025-X
M3 - Article
C2 - 11384737
AN - SCOPUS:0034983856
SN - 0065-2571
VL - 41
SP - 57
EP - 71
JO - Advances in Enzyme Regulation
JF - Advances in Enzyme Regulation
IS - 1
ER -