The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity

Jeannette Kunz, Monita P. Wilson, Marina Kisseleva, James H. Hurley, Philip W. Majerus, Richard A. Anderson

Research output: Contribution to journalArticle

116 Citations (Scopus)

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 languageEnglish
Pages (from-to)1-11
Number of pages11
JournalMolecular Cell
Volume5
Issue number1
Publication statusPublished - Jan 2000
Externally publishedYes

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Phosphatidylinositol Phosphates
Phosphotransferases
Phosphatidylinositols
Eukaryotic Cells
Catalytic Domain
Cell Survival
Cell Proliferation
Amino Acids
Membranes

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Kunz, J., Wilson, M. P., Kisseleva, M., Hurley, J. H., Majerus, P. W., & Anderson, R. A. (2000). The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Molecular Cell, 5(1), 1-11.

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 journalArticle

Kunz, J, Wilson, MP, Kisseleva, M, Hurley, JH, Majerus, PW & Anderson, RA 2000, 'The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity', Molecular Cell, vol. 5, no. 1, pp. 1-11.
Kunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, Anderson RA. The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Molecular Cell. 2000 Jan;5(1):1-11.
Kunz, Jeannette ; Wilson, Monita P. ; Kisseleva, Marina ; Hurley, James H. ; Majerus, Philip W. ; Anderson, Richard A. / The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. In: Molecular Cell. 2000 ; Vol. 5, No. 1. pp. 1-11.
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