Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Molecular Cell |
| Volume | 5 |
| Issue number | 1 |
| Publication status | Published - Jan 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
Cite this
The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. / Kunz, Jeannette; Wilson, Monita P.; Kisseleva, Marina; Hurley, James H.; Majerus, Philip W.; Anderson, Richard A.
In: Molecular Cell, Vol. 5, No. 1, 01.2000, p. 1-11.Research output: Contribution to journal › Article
}
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.
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.
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M3 - Article
VL - 5
SP - 1
EP - 11
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 1
ER -