We had previously shown that murine macrophages expressing v-Fes, the oncogenically activated counterpart of the c-Fes cytoplasmic tyrosine kinase, proliferate independently of Macrophage Colony-Stimulating Factor (MCSF) and that the Extracellular signal-Regulated Kinase (ERK) pathway mediates the mitogenic effect of v-Fes. In this study, the response of c-fes- and v-fes-overexpressing cells to MCSF was investigated. A critical modulation of the activation of Mitogen-activated ERK Kinase (MEK) and ERK based on the MCSF dose was characterized. ERK activation was increased by MCSF doses capable to elicit a mitogenic response (2-5 U/ml). On the contrary, MCSF doses as low as 0.05 U/ml markedly reduced ERK phosphorylation and nuclear content and moderately but significantly reduced cell proliferation. The reduction of MEK and ERK phosphorylation was very rapid, suggesting the involvement of cytosolic phosphatases. Among these, phospho-tyrosine protein phosphatases and phosphoserine/threonine protein phosphatase-2A were found involved. These findings represent the first observation that different doses of the same growth factor, MCSF in particular, can exert opposite effects on cell proliferation by switching on or off ERK signaling.
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http://dx.doi.org/10.1038/sj.onc.1205409 | DOI Listing |
J Biol Chem
January 2025
Department of Biological Sciences, Moravian University, 1200 Main Street, Bethlehem, PA 18018, USA. Electronic address:
Phosphorylation of connexin 43 (Cx43) is an important regulatory mechanism of gap junction (GJ) function. Cx43 is modified by several kinases on over 15 sites within its ∼140 amino acid-long C-terminus (CT). Phosphorylation of Cx43CT on S255, S262, S279, and S282 by ERK has been widely documented in several cell lines, by many investigators.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA. Electronic address:
Extracellular matrix stiffness is one of the multiple mechanical signals that alters cellular behavior. During studies exploring the effect of matrix rigidity on lung fibroblast survival we discovered that enhanced survival on stiff substrates is dependent on elevated Ras activity, owing to the activation of the GEF, RasGRF1. Mechanistically, we found that the increased Ras activity lead to the activation of both the AKT and ERK pathways.
View Article and Find Full Text PDFJ Neurochem
January 2025
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Severe trauma frequently leads to nerve damage. Peripheral nerves possess a degree of regenerative ability, and actively promoting their recovery can help restore the sensory and functional capacities of tissues. The neuropeptide calcitonin gene-related peptide (CGRP) is believed to regulate the repair of injured peripheral nerves, with neuronal transient receptor potential vanilloid type 1 (TRPV1) potentially serving as a crucial upstream factor.
View Article and Find Full Text PDFCell Rep
January 2025
Genetics and Epigenetics Program, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Genetics, University of Texas MD Anderson Cancer Center and The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address:
ERK activity oscillates between sustained activation during oocyte formation and transient inactivation during oocyte maturation, fertilization, and early embryogenesis. Consequences of ectopic ERK activity upon oocyte maturation and in early embryogenesis are unknown. We show, in Caenorhabditis elegans, that ectopic ERK activity upon oocyte maturation (metaphase I oocytes) results in embryos with abnormalities in nuclear divisions leading to embryonic death.
View Article and Find Full Text PDFMol Neurobiol
January 2025
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Approaches of promoting a neural milieu permissive for plasticity and resilience against neuronal injury are important strategies for the treatment of a range of neurological disorders. Fibroblast growth factor 21 (FGF21) which is known for its role as a potent regulator of glucose and energy metabolism has also proved to be neuroprotective against various mental diseases. However, the underlying molecular mechanisms remain elusive.
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