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Cited by 566Protein Kinase Regulation and GTPase SignalingCellular transport and secretionLipid Membrane Structure and Behavior

Specific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain

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Lemmon, M A, Ferguson, K M, O'Brien, R, Sigler, P B, Schlessinger, J·1995·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.92.23.10472PMC PMC40633
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Abstract

Pleckstrin homology (PH) domains are found in many signaling molecules and are thought to be involved in specific intermolecular interactions. Their binding to several proteins and to membranes containing 1-alpha-phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has been reported. A region that includes the PH domain has also been implicated in binding of phospholipase C-delta 1 (PLC-delta 1) to both PtdIns(4,5)P2 and D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] [Cifuentes, M. E., Delaney, T. & Rebecchi, M. J. (1994) J. Biol. Chem. 269, 1945-1948]. We report herein that the isolated PH domain from PLC-delta 1 binds to both PtdIns(4,5)P2 and Ins(1,4,5)P3 with high affinity and shows the same binding specificity seen by others with whole PLC-delta 1. Thus the PH domain is functionally and structurally modular. These results demonstrate stereo-specific high-affinity binding by an isolated PH domain and further support a functional role for PH domains in the regulation of PLC isoforms. Other PH domains did not bind strongly to the compounds tested, suggesting that inositol phosphates and phospholipids are not likely physiological ligands for all PH domains. Nonetheless, since all PH-domain-containing proteins are associated with membrane surfaces, several PH domains bind to specific sites on membranes, and PH domains appear to be electrostatically polarized, a possible general role for PH domains in membrane association is suggested.

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  • The PH domain of PLCδ binds to 4,5-PIP2 in vitro and in vivo with high affinity and specificity.

    “The PH domain of PLCδ was shown to bind to 4,5-PIP2 in vitro and in vivo with high affinity and specificity (Lemmon et al. 1995).”

    From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Lemmon et al. 1995

    The Abstract reports that the isolated PLCδ1 PH domain binds PtdIns(4,5)P2 with high affinity and specificity. It does not report binding demonstrated in vivo, so the cited paper supports the binding claim but not that setting. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • PLCδ-PH-GFP is a specific probe for 4,5-PIP2 in macrophages.

    “PLCδ-PH-GFP Is a Specific Probe for 4,5-PIP2 in Macrophages”

    From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Lemmon et al. 1995

    The Abstract reports that the isolated PLCδ1 PH domain binds PtdIns(4,5)P2 with high affinity and binding specificity. It does not evaluate a GFP-tagged probe or establish that it specifically detects PtdIns(4,5)P2 in macrophages; it also reports binding to Ins(1,4,5)P3. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 35

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Sorted by citations

Authors
Lemmon, M. A., Ferguson, K. M., O'Brien, R., Sigler, P. B., & Schlessinger, J.
Affiliations
  • NYU Langone Health (US)
  • Department of Pharmacology, New York University Medical Center, New York 10016, USA.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1995-11-07
Volume
92
Issue
23
Pages
10472-10476
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.92.23.10472
PMC
PMC40633
OpenAlex
W1997784032
Cited by
566
References
0
Citations by year
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FWCI
12.28
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Damon Runyon Cancer Research Foundation
  • Yale University
  • National Institutes of Health (5r01gm004725-40, GM 04725)
  • National Institute of General Medical Sciences (GM22342, GM-04725)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
pleckstrin homology domain, inositol phosphates, phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate, phospholipase C delta 1, ligand specificity, membrane association, membrane polarization, phospholipase C isoforms
MeSH terms
Amino Acid Sequence, Animals, Binding, Competitive, Blood Proteins, Calorimetry, Inositol Phosphates, Isoenzymes, Molecular Sequence Data, Peptide Fragments, Type C Phospholipases, Phosphoproteins, Inositol 1,4,5-Trisphosphate, Sequence Homology, Amino Acid, Phosphatidylinositol Phosphates, Phosphatidylinositol 4,5-Diphosphate, Rats, Phospholipase C delta

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