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Cited by 103Streptococcal Infections and TreatmentsProtein Kinase Regulation and GTPase SignalingBacterial Genetics and Biotechnology

Regulation of the Phosphorylation of Human Pharyngeal Cell Proteins by Group A Streptococcal Surface Dehydrogenase: Signal Transduction between Streptococci and Pharyngeal Cells

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Pancholi, Vijaykumar, Fischetti, Vincent A.·1997·The Journal of Experimental Medicine
DOI 10.1084/jem.186.10.1633PMC PMC2199133
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Abstract

Whether cell-to-cell communication results when group A streptococci interact with their target cells is unknown. Here, we report that upon contact with cultured human pharyngeal cells, both whole streptococci and purified streptococcal surface dehydrogenase (SDH) activate pharyngeal cell protein tyrosine kinase as well as protein kinase C, thus regulating the phosphorylation of cellular proteins. SDH, a major surface protein of group A streptococci, has both glyceraldehyde-3-phosphate dehydrogenase and ADP-ribosylating enzyme activities that may relate to early stages of streptococcal infection. Intact streptococci and purified SDH induce a similar protein phosphorylation pattern with the de novo tyrosine phosphorylation of a 17-kD protein found in the membrane/particulate fraction of the pharyngeal cells. However, this phosphorylation required the presence of cytosolic components. NH2-terminal amino acid sequence analysis identified the 17-kD protein as nuclear core histone H3. Both phosphotyrosine and phosphoserine-specific monoclonal antibodies reacted with the 17-kD protein by Western blot, suggesting that the binding of SDH to these pharyngeal cells elicits a novel signaling pathway that ultimately leads to activation of histone H3–specific kinases. Genistein-inhibitable phosphorylation of histone H3 indicates that tyrosine kinase plays a key role in this event. Treatment of pharyngeal cells with protein kinase inhibitors such as genistein and staurosporine significantly inhibited streptococcal invasion of pharyngeal cells. Therefore, these data indicated that streptococci/SDH-mediated phosphorylation plays a critical role in bacterial entry into the host cell. To identify the membrane receptor that elicits these signaling events, we found that SDH bound specifically to 30- and 32-kD membrane proteins in a direct ligand-binding assay. These findings clearly suggest that SDH plays an important role in cellular communication between streptococci and pharyngeal cells that may be important in host cell gene transcription, and hence in the pathogenesis of streptococcal infection.

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  • Reassociation of anchorless adhesins and invasins occurs in Streptococcus pyogenes.

    “(vi) Reassociation of anchorless adhesins and invasins (in Streptococcus pyogenes) [14].”

    From Protein sorting to the cell wall envelope of Gram-positive bacteria (2004) · cites this paper as [14]

    The Abstract describes surface dehydrogenase (SDH) on group A streptococci, and the Results section on streptococcal adherence and invasion examines their interaction with pharyngeal cells; page numbers are not available in our copy. Neither passage establishes that anchorless adhesins or invasins leave and reassociate with the bacterial surface. Searches for reassociation, anchoring, and rebinding found no passage addressing that process. (LLM, conf=0.74)

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  1. [9]Kehoe, M.A. 1994. Cell-wall-associated proteins in gram-positive bacteria. In Bacterial Cell Wall. J.-M. Ghuysen and R. Hakenbeck, editors. Elsevier Science, Amsterdam. 217– 261.

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Authors
Pancholi, V., & Fischetti, V. A.
Affiliations
  • From the Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, New York 10021
  • Rockefeller University (US)
ORCID
Fischetti, Vincent A.
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
1997-11-17
Volume
186
Issue
10
Pages
1633-1643
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.186.10.1633
PMC
PMC2199133
OpenAlex
W2122514491
Cited by
103
References
46
Citations by year
2023: 3 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 6 · 2012: 7
FWCI
5.07
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (10021)
  • National Institute of Allergy and Infectious Diseases (AI-11822, R01AI011822, R37AI011822)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Streptococcal Infections and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Streptococcus pyogenes, tyrosine kinase, protein kinase C, protein phosphorylation, cell-to-cell communication, cell surface receptors, genistein, staurosporine, glyceraldehyde-3-phosphate dehydrogenase
MeSH terms
Amino Acid Sequence, Bacterial Adhesion, Bacterial Proteins, Carcinoma, Squamous Cell, Cell Fractionation, Cell Survival, Cytosol, Glyceraldehyde-3-Phosphate Dehydrogenases, Histones, Humans, Membrane Proteins, Molecular Sequence Data, Molecular Weight, Pharyngeal Neoplasms, Pharynx, Phosphoproteins, Phosphorylation, Receptors, Cell Surface, Streptococcus pyogenes, Tumor Cells, Cultured, Signal Transduction

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