TY - JOUR
T1 - A conspicuous connection
T2 - Structure defines function for the phosphatidylinositol-phosphate kinase family
AU - Heck, Jessica N.
AU - Mellman, David L.
AU - Ling, Kun
AU - Sun, Yue
AU - Wagoner, Matthew P.
AU - Schill, Nicholas J.
AU - Anderson, Richard A.
N1 - Funding Information:
We would like to thank Kenneth Satyshur for molecular modeling expertise. We are grateful to Matthew W. Bunce, Michael L. Gonzales, and Lisa N. Christianson for comments on the manuscript. Research in the authors’ laboratory is supported by NIH grants GM057549, GM051968, and CA104708 to R.A.A. J.N.H., D.L.M., and M.P.W. are supported by the NIH training grant in Molecular and Cellular Pharmacology T32 GM08688. K.L. is supported by American Heart Association (AHA) fellowship #0425731Z and AHA National Scientist Development Grant #0535552 N. Y.S. is supported by AHA Postdoctoral fellowship #05201212. N.J.S. is supported by AHA Predoctoral fellowship #133JA83.
PY - 2007/1
Y1 - 2007/1
N2 - The phosphatidylinositol phosphate (PIP) kinases are a unique family of enzymes that generate an assortment of lipid messengers, including the pivotal second messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2). While members of the PIP kinase family function by catalyzing a similar phosphorylation reaction, the specificity loop of each PIP kinase subfamily determines substrate preference and partially influences distinct subcellular targeting. Specific protein-protein interactions that are unique to particular isoforms or splice variants play a key role in targeting PIP kinases to appropriate subcellular compartments to facilitate the localized generation of PI4,5P2 proximal to effectors, a mechanism key for the function of PI4,5P2 as a second messenger. This review documents the discovery of the PIP kinases and their signaling products, and summarizes our current understanding of the mechanisms underlying the localized generation of PI4,5P2 by PIP kinases for the regulation of cellular events including actin cytoskeleton dynamics, vesicular trafficking, cell migration, and an assortment of nuclear events.
AB - The phosphatidylinositol phosphate (PIP) kinases are a unique family of enzymes that generate an assortment of lipid messengers, including the pivotal second messenger phosphatidylinositol 4,5-bisphosphate (PI4,5P2). While members of the PIP kinase family function by catalyzing a similar phosphorylation reaction, the specificity loop of each PIP kinase subfamily determines substrate preference and partially influences distinct subcellular targeting. Specific protein-protein interactions that are unique to particular isoforms or splice variants play a key role in targeting PIP kinases to appropriate subcellular compartments to facilitate the localized generation of PI4,5P2 proximal to effectors, a mechanism key for the function of PI4,5P2 as a second messenger. This review documents the discovery of the PIP kinases and their signaling products, and summarizes our current understanding of the mechanisms underlying the localized generation of PI4,5P2 by PIP kinases for the regulation of cellular events including actin cytoskeleton dynamics, vesicular trafficking, cell migration, and an assortment of nuclear events.
KW - Lipid messengers
KW - PIP kinase structure
KW - Phosphatidylinositol 4,5-bisphosphate (PI4,5P)
KW - Phosphoinositide signaling
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U2 - 10.1080/10409230601162752
DO - 10.1080/10409230601162752
M3 - Review article
C2 - 17364683
AN - SCOPUS:33847772690
SN - 1040-9238
VL - 42
SP - 15
EP - 39
JO - Critical Reviews in Biochemistry and Molecular Biology
JF - Critical Reviews in Biochemistry and Molecular Biology
IS - 1
ER -