TY - JOUR
T1 - The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity
AU - Kunz, Jeannette
AU - Wilson, Monita P.
AU - Kisseleva, Marina
AU - Hurley, James H.
AU - Majerus, Philip W.
AU - Anderson, Richard A.
N1 - Funding Information:
The technical assistance of Mary-Ann Watts is greatly acknowledged. We thank P. Baas and members of his lab for use of their fluorescence microscope and digital camera, M. N. Hall and T. Beck for the gift of yeast strains and plasmids, and G. Halder for critically reading of the manuscript. This work was supported by National Institutes of Health grants (R. A. A. and P. W. M.) and a Swiss Advanced Postdoctoral National Foundation Grant (J. K.).
PY - 2000/1
Y1 - 2000/1
N2 - Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant. Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels.
AB - Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant. Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels.
UR - http://www.scopus.com/inward/record.url?scp=0033969444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033969444&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(00)80398-6
DO - 10.1016/S1097-2765(00)80398-6
M3 - Article
C2 - 10678164
AN - SCOPUS:0033969444
VL - 5
SP - 1
EP - 11
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 1
ER -