Inhibition of β2 Integrin Receptor and Syk Kinase Signaling in Monocytes by the Src Family Kinase Fgr
Open accessAbstract
While beta 2 integrin ligand-receptor recognition interactions are well characterized, less is known about how these events trigger signal transduction cascades to regulate the transition from tethering to firm adhesion, spreading, and transendothelial migration. We have identified critical positive and negative regulatory components of this cascade in monocytes. Whereas the Syk tyrosine kinase is essential for beta 2 integrin signaling and cell spreading, the Src family kinase Fgr is a negative regulator of this pathway. Fgr selectively inhibits beta 2 but not beta 1 integrin signaling and Syk kinase function via a direct association between the Fgr SH2 domain and Syk tyrosine Y342. The inhibitory effects of Fgr are independent of its kinase activity, are dose dependent, and can be overcome by chemokines and inflammatory mediators.
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Integrin-mediated activation of monocytes requires SYK.
“It is known that integrin-mediated activation of monocytes requires SYK35”
From PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages (2021) · cites this paper as [35]
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- Authors
- Vines, C. M., Potter, J. W., Xu, Y., Geahlen, R. L., Costello, P. S., Tybulewicz, V. L., Lowell, C. A., Chang, P. W., Gresham, H. D., & Willman, C. L.
- Affiliations
- University of New Mexico (US)
- Purdue University West Lafayette (US)
- National Institute for Medical Research (GB)
- University of California, San Francisco (US)
- Corresponding author
- Willman, Cheryl L
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2001-10
- Volume
- 15
- Issue
- 4
- Pages
- 507-519
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2065197757
- Cited by
- 87
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2016: 5 · 2015: 3 · 2014: 3 · 2012: 5
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk043042-05, 5p01dk050267-05)
- National Heart, Lung, and Blood Institute (HL54467)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 50267, DK43042)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- Fgr, Syk, Src family kinases, monocytes, SH2 domain, cell spreading, transendothelial migration, firm adhesion, chemokines, inflammatory mediators
- MeSH terms
- Syk Kinase, Animals, Cell Adhesion, Cell Line, Cells, Cultured, Enzyme Precursors, Macrophages, Monocytes, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Transfection, Signal Transduction, Mice, Knockout, CD18 Antigens, src Homology Domains, Chemokines, src-Family Kinases, Intracellular Signaling Peptides and Proteins, Cell Size, Mice, Proto-Oncogene Proteins c-hck
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