ArticleThe Journal of biological chemistry2009
B cell receptor-induced phosphorylation of Pyk2 and focal adhesion kinase involves integrins and the Rap GTPases and is required for B cell spreading.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 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
- MIZ-1 controls transcriptional programs required for BCR signaling, actin dynamics, and naïve B cell survival.Frontiers in immunology · 2026Article
- SRC and ERK Regulate the Turnover of Cytoskeletal Keratin Filaments.International journal of molecular sciences · 2025Article
- Discrete-state models identify pathway specific B cell states across diseases and infections at single-cell resolution.Journal of theoretical biology · 2024Article
- B cell mechanosensing regulates ER remodeling at the immune synapse.Frontiers in immunology · 2024Article
- Mercury intoxication disrupts tonic signaling in B cells, and may promote autoimmunity due to abnormal phosphorylation of STIM-1 and other autoimmunity risk associated phosphoproteins involved in BCR signaling.Toxicology and applied pharmacology · 2023Article
- Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression.Blood advances · 2023Article
- Review
- Review
- A loss-of-adhesion CRISPR-Cas9 screening platform to identify cell adhesion-regulatory proteins and signaling pathways.Nature communications · 2022Article
- Review
- Review
- Rap2B promotes cell proliferation, migration and invasion in prostate cancer.Medical oncology (Northwood, London, England) · 2016Article
- The WNT signaling pathway contributes to dectin-1-dependent inhibition of Toll-like receptor-induced inflammatory signature.Molecular and cellular biology · 2014Article
- Control of dendritic cell migration, T cell-dependent immunity, and autoimmunity by protein tyrosine phosphatase PTPN12 expressed in dendritic cells.Molecular and cellular biology · 2014Article
- Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia.Nature immunology · 2014Article
- N-ethylmaleimide-sensitive factor attachment protein α (αSNAP) regulates matrix adhesion and integrin processing in human epithelial cells.The Journal of biological chemistry · 2014Article
- Focal adhesion kinase negatively regulates Lck function downstream of the T cell antigen receptor.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Macrophage fusion is controlled by the cytoplasmic protein tyrosine phosphatase PTP-PEST/PTPN12.Molecular and cellular biology · 2013Article
- Visualizing and manipulating focal adhesion kinase regulation in live cells.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling by the B cell receptor (BCR) promotes integrin-mediated adhesion and cytoskeletal reorganization. This results in B cell spreading, which enhances the ability of B cells to bind antigens and become activated. Proline-rich tyrosine kinase (Pyk2) and focal adhesion kinase (FAK) are related cytoplasmic tyrosine kinases that regulate cell adhesion, cell morphology, and cell migration. In this report we show that BCR signaling and integrin signaling collaborate to induce the phosphorylation of Pyk2 and FAK on key tyrosine residues, a modification that increases the kinase activity of Pyk2 and FAK. Activation of the Rap GTPases is critical for BCR-induced integrin activation as well as for BCR- and integrin-induced reorganization of the actin cytoskeleton. We now show that Rap activation is essential for BCR-induced phosphorylation of Pyk2 and for integrin-induced phosphorylation of Pyk2 and FAK. Moreover Rap-dependent phosphorylation of Pyk2 and FAK required an intact actin cytoskeleton as well as actin dynamics, suggesting that Rap regulates Pyk2 and FAK via its effects on the actin cytoskeleton. Importantly B cell spreading induced by BCR/integrin co-stimulation or by integrin engagement was inhibited by short hairpin RNA-mediated knockdown of either Pyk2 or FAK expression and by treatment with PF-431396, a chemical inhibitor that blocks the kinase activities of both Pyk2 and FAK. Thus Pyk2 and FAK are downstream targets of the Rap GTPases that play a key role in regulating B cell morphology.
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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.