Fibroblast growth factor 2 (FGF-2) has been detected in the nuclei of many tissues and cell lines. Here we demonstrate that FGF-2 added exogenously to NIH3T3 cells enters the nucleus and interacts with the nuclear active 90-kDa ribosomal S6 kinase 2 (RSK2) in a cell cycle-dependent manner. By using purified proteins, FGF-2 is shown to directly interact through two separate domains with two RSK2 domains on both sides of the hydrophobic motif, namely the NH2-terminal kinase domain (residues 360-381) by amino acid Ser-117 and the COOH-terminal kinase domain (residues 388-400) by amino acids Leu-127 and Lys-128. Moreover, this interaction leads to maintenance of the sustained activation of RSK2 in G1 phase of the cell cycle. FGF-2 mutants (FGF-2 S117A, FGF-2 L127A, and FGF-2 K128A) that fail to interact in vitro with RSK2 fail to maintain a sustained RSK2 activity in vivo.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M500232200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinicopathological and in Silico Insights into Male Infertility: Agerelated Trends and Anti-sperm Antibodies Post COVID-19 Vaccination.
Curr Med Chem
January 2025
Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Background: Infertility was often considered a female issue, but male infertility emerged significantly after the Covid-19 pandemic. Hence, assessments are crucial for planning policies on health care and family planning and reasons thereof post vaccinations.
Material And Methods: The present study was a case-control, dual-centers, prospective study with normal sperm parameters.
Implication of fibroblast growth factor 7 in ovarian cancer metastases and patient survival.
Front Oncol
January 2025
Gynecologic Oncology Section, Stephenson Cancer Center, Obstetrics and Gynecology Department, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Background/objectives: Patients with ovarian cancer commonly experience metastases and recurrences, which contribute to high mortality. Our objective was to better understand ovarian cancer metastasis and identify candidate biomarkers and drug targets for predicting and preventing ovarian cancer recurrence.
Methods: Transcripts of 770 cancer-associated genes were compared in cells collected from ascitic fluid versus resected tumors of an ES-2 orthotopic ovarian cancer mouse model.
Enter the Matrix: Fibroblast-immune cell interactions shape extracellular matrix deposition in health and disease.
F1000Res
January 2025
Immunology, University of Toronto, Toronto, Ontario, Canada.
Fibroblasts, non-hematopoietic cells of mesenchymal origin, are tissue architects which regulate the topography of tissues, dictate tissue resident cell types, and drive fibrotic disease. Fibroblasts regulate the composition of the extracellular matrix (ECM), a 3-dimensional network of macromolecules that comprise the acellular milieu of tissues. Fibroblasts can directly and indirectly regulate immune responses by secreting ECM and ECM-bound molecules to shape tissue structure and influence organ function.
View Article and Find Full Text PDFPotential implications of granzyme B in keloids and hypertrophic scars through extracellular matrix remodeling and latent TGF-β activation.
Front Immunol
January 2025
International Collaboration on Repair Discoveries (ICORD) Centre, Vancouver Coastal Health Research Institute (VCHRI), University of British Columbia (UBC), Vancouver, BC, Canada.
Keloid scars (KS) and hypertrophic scars (HS) are fibroproliferative wound healing defects characterized by excessive accumulation of extracellular matrix (ECM) in the dermis of affected individuals. Although transforming growth factor (TGF)-β is known to be involved in the formation of KS and HS, the molecular mechanisms responsible for its activation remain unclear. In this study we investigated Granzyme B (GzmB), a serine protease with established roles in fibrosis and scarring through the cleavage of ECM proteins, as a potential new mediator of TGF-β activation in KS and HS.
View Article and Find Full Text PDFDiscovery of Pyrrolopyrazine Carboxamide Derivatives as Potent and Selective FGFR2/3 Inhibitors that Overcome Mutant Resistance.
J Med Chem
January 2025
Insilico Medicine Shanghai Ltd, Suite 901, Tower C, Changtai Plaza, 2889 Jinke Road, Pudong New District, Shanghai 201203, China.
Fibroblast growth factor receptors (FGFRs) are established oncogenic drivers in various solid tumors. However, the approved FGFR inhibitors face challenges with acquired resistance and dose-limiting adverse effects associated with FGFR1/4 inhibition, limiting therapeutic efficacy. Herein, we systematically explored linker and electrophile moieties based on the pyrrolopyrazine carboxamide core and identified aniline α-fluoroacrylamide as an effective covalent warhead.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!