ArticleBiochemical pharmacology2013
The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ T cell activation.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Proline-rich tyrosine kinase 2 controls PI3-kinase activation downstream of the T cell antigen receptor in human T cells.Journal of leukocyte biology · 2015Trial
- Article
- A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025).Frontiers in bioengineering and biotechnology · 2026Review
- Razing the scaffolding: the elimination of non-catalytic functions of kinases through targeted protein degradation.RSC medicinal chemistry · 2025Review
- Focal adhesion kinase plays an essential role in Th17 cell differentiation by stimulating NF-κB signaling.Frontiers in immunology · 2025Article
- New Insights on the Nuclear Functions and Targeting of FAK in Cancer.International journal of molecular sciences · 2022Review
- Network-based approach for targeting human kinases commonly associated with amyotrophic lateral sclerosis and cancer.Frontiers in molecular neuroscience · 2022Article
- Targeting FAK in anticancer combination therapies.Nature reviews. Cancer · 2021Review
- Review
- Review
- Focal adhesion kinase (FAK) phosphorylation is a key regulator of embryonal rhabdomyosarcoma (ERMS) cell viability and migration.Journal of cancer research and clinical oncology · 2019Article
- CX3CL1/fractalkine enhances prostate cancer spinal metastasis by activating the Src/FAK pathway.International journal of oncology · 2018Article
- Geranylgeranyl diphosphate synthase inhibition induces apoptosis that is dependent upon GGPP depletion, ERK phosphorylation and caspase activation.Cell death & disease · 2017Article
- Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer.Molecular cancer therapeutics · 2016Article
- Focal adhesion kinase is required for synovial fibroblast invasion, but not murine inflammatory arthritis.Arthritis research & therapy · 2014Article
- Functions of the FAK family kinases in T cells: beyond actin cytoskeletal rearrangement.Immunologic research · 2014Review
- Focal adhesion kinase negatively regulates Lck function downstream of the T cell antigen receptor.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The focal adhesion kinase inhibitor, PF-562,271, is currently in clinical development for cancer, however it is not known how PF-562,271 affects T cell function. Here, we demonstrate inhibitory effects of PF-562,271 on the activation of primary human and mouse T cells. PF-562,271 inhibits T cell receptor signaling-induced T cell adhesion to intercellular adhesion molecule-1 and T cell interactions with antigen-presenting cells. An additional focal adhesion kinase inhibitor, PF-573,228, and genetic depletion of focal adhesion kinase also impair T cell conjugation with antigen-presenting cells. PF-562,271 blocks phosphorylation of the signaling molecules zeta chain associate protein of 70 kDa, linker of activated T cells, and extracellular signal-regulated kinase, and impairs T cell proliferation. The effects observed on T cell proliferation cannot solely be attributed to focal adhesion kinase inhibition, as genetic depletion did not alter proliferation. The effect of PF-562,271 on T cell proliferation is not rescued when proximal T cell receptor signaling is bypassed by stimulation with phorbol-12-myristate-13-acetate and ionomycin. Taken together, our findings demonstrate that focal adhesion kinase regulates integrin-mediated T cell adhesion following T cell receptor activation. Moreover, our findings suggest that PF-562,271 may have immunomodulatory effects that could impact its therapeutic applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.