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Cited by 40Protein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancerCellular transport and secretion

Proteomic identification of phosphatidylinositol (3,4,5) triphosphate-binding proteins in Dictyostelium discoideum

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Zhang, Pingbo, Wang, Yu, Sesaki, Hiromi, Iijima, Miho·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1006153107PMC PMC2900710
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Abstract

Phosphatidylinositol (3,4,5)-triphosphate (PtdInsP 3 ) mediates intracellular signaling for directional sensing and pseudopod extension at the leading edge of migrating cells during chemotaxis. How this PtdInsP 3 signal is translated into remodeling of the actin cytoskeleton is poorly understood. Here, using a proteomics approach, we identified multiple PtdInsP 3 -binding proteins in Dictyostelium discoideum , including five pleckstrin homology (PH) domain-containing proteins. Two of these, the serine/threonine kinase Akt/protein kinase B and the PH domain-containing protein PhdA, were previously characterized as PtdInsP 3 -binding proteins. In addition, PhdB, PhdG, and PhdI were identified as previously undescribed PH domain-containing proteins. Specific PtdInsP 3 interactions with PhdB, PhdG, and PhdI were confirmed using an in vitro lipid-binding assay. In cells, PhdI associated with the plasma membrane in a manner dependent on both the PH domain and PtdInsP 3 . Consistent with this finding, PhdI located to the leading edge in migrating cells. In contrast, PhdG was found in the cytosol in WT cells. However, when PtdInsP 3 was overproduced in pten − cells, PhdG located to the plasma membrane, suggesting its weak affinity for PtdInsP 3 . PhdB was found to bind to the plasma membrane via both PtdInsP 3 -dependent and -independent mechanisms. The PtdInsP 3 -independent interaction was mediated by the middle domain, independent of the PH domain. In migrating cells, the majority of PhdB was found at the lagging edge. Finally, we deleted the genes encoding PhdB and PhdG and demonstrated that both proteins are required for efficient chemotaxis. Thus, this study advances our understanding of the PtdInsP 3 -mediated signaling mechanisms that control directed cell migration in chemotaxis.

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  • PI(3,4,5)P3 and its derivative PI(3,4)P2 interact with the lipid-binding PH domain in a range of protein effectors, resulting in their recruitment to membrane-signalling complexes and/or modulation of their activity.

    “PI(3,4,5)P3 and PI(3,4)P2 interact with the lipid-binding PH-domain in a range of protein effectors, resulting in their recruitment to membrane-signalling complexes and/or modulation of their activity [78–81].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [79]

    The Discussion describes PH-domain proteins as a major group of PtdInsP3-binding proteins, and the Results show PtdInsP3-dependent recruitment of several proteins to the plasma membrane. The Results also say that PHcrac binds PtdIns(3,4)P2, but do not establish that this lipid recruits or modulates a range of effectors. Page numbers were not supplied. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Zhang, P., Wang, Y., Sesaki, H., & Iijima, M.
Affiliations
Johns Hopkins University (US)
Corresponding author
Iijima, Miho
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2010-06-14
Volume
107
Issue
26
Pages
11829-11834
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1006153107
PMC
PMC2900710
OpenAlex
W2128095861
Cited by
40
References
1
Citations by year
2025: 2 · 2024: 2 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 2 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 6 · 2012: 4
FWCI
1.56
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • Muscular Dystrophy Association
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM-084015, R01GM084015)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
pleckstrin homology domain, Dictyostelium discoideum, chemotaxis, cell migration, actin cytoskeleton remodeling, Akt/protein kinase B, plasma membrane binding, PTEN
MeSH terms
Cyclic AMP, Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Membrane, Chemotaxis, Dictyostelium, Molecular Sequence Data, Movement, Signal Transduction, Protozoan Proteins, DNA, Protozoan, Protein Structure, Tertiary, Phosphatidylinositol Phosphates, Proteomics, Proto-Oncogene Proteins c-akt

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