Pyk2 (proline-rich tyrosine kinase 2) and FAK (focal adhesion kinase) are highly related tyrosine kinases. One distinguishing feature is the differential regulation of the two enzymes in response to elevation of cytoplasmic calcium. In the latest issue of the Biochemical Journal, Sasaki and co-workers have provided insight into the calcium-dependent regulation of Pyk2. The findings suggest that calmodulin may bind the FERM (4.1/ezrin/radixin/moesin) domain to promote Pyk2 activation in response to calcium signals triggered by vasopressin. While the molecular details of the protein-protein interaction and mechanism of activation remain to be firmly established, this study is the first to provide mechanistic insight into the regulation of Pyk2 by calcium.
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http://dx.doi.org/10.1042/BJ20080133 | DOI Listing |
Cells
November 2024
Department of Biomedical and Community Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
CD38, a nicotinamide adenine dinucleotide (NAD) glycohydrolase, increases during infection or inflammation. Therefore, we aimed to evaluate the effects of a CD38 inhibitor (78c) on NAD levels, IL-1β, IL-6, TNF-α cytokine expressions, and osteoclastogenesis. The results show that treatment with 78c on murine BMMs dose-dependently reduced CD38, reversed the decline of NAD, and inhibited IL-1β, IL-6, and TNF-α pro-inflammatory cytokine levels induced by oral pathogen () or () or by advanced glycation end products (AGEs).
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China.
Dysfunction of calcium channels is involved in the development and progression of some cancers. However, it remains unclear the role of calcium channel inhibitors in tumor immunomodulation. Here, calcium channel blocker lacidipine is identified to potently inhibit the enzymatic activity and expression of indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism.
View Article and Find Full Text PDFCell Commun Signal
November 2024
Department of Oral Pathobiological Science, Microbiology, Graduate School of Dental Medicine, Hokkaido University, Kita13 Nishi7, Kita-Ku, Sapporo, 060-8586, Japan.
Understanding the intricate cellular interactions involved in bone restoration is crucial for developing effective strategies to promote bone healing and mitigate conditions such as osteoporosis and fractures. Here, we provide compelling evidence supporting the anabolic effects of a pharmacological Pyk2 inhibitor (Pyk2-Inh) in promoting bone restoration. In vitro, Pyk2 signaling inhibition markedly enhances alkaline phosphatase (ALP) activity, a hallmark of osteoblast differentiation, through activation of canonical Wnt/β-catenin signaling.
View Article and Find Full Text PDFUnlabelled: Focal adhesion kinase (FAK) functions as a signaling and scaffolding protein within endothelial cells (ECs) impacting blood vessel function and tumor growth. Interpretations of EC FAK-null phenotypes are complicated by related PYK2 (protein tyrosine kinase 2) expression, and to test this, we created PYK2 FAK mice with tamoxifen-inducible EC-specific Cre recombinase expression. At 11 weeks of age, EC FAK inactivation resulted in increased heart and lung mass and vascular leakage only on a PYK2 background.
View Article and Find Full Text PDFCancer Gene Ther
November 2024
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Multiple myeloma (MM), a hematological malignancy of plasma cells, has remained largely incurable owing to drug resistance and disease relapse, which requires novel therapeutic targets and treatment approaches. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) acts as an oncoprotein linked to the development of various tumors. However, the functional consequence of Pin1 overexpression in modulating MM biology has not been established.
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