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Cell Nov 2006Cell signaling mechanisms often transmit information via posttranslational protein modifications, most importantly reversible protein phosphorylation. Here we develop...
Cell signaling mechanisms often transmit information via posttranslational protein modifications, most importantly reversible protein phosphorylation. Here we develop and apply a general mass spectrometric technology for identification and quantitation of phosphorylation sites as a function of stimulus, time, and subcellular location. We have detected 6,600 phosphorylation sites on 2,244 proteins and have determined their temporal dynamics after stimulating HeLa cells with epidermal growth factor (EGF) and recorded them in the Phosida database. Fourteen percent of phosphorylation sites are modulated at least 2-fold by EGF, and these were classified by their temporal profiles. Surprisingly, a majority of proteins contain multiple phosphorylation sites showing different kinetics, suggesting that they serve as platforms for integrating signals. In addition to protein kinase cascades, the targets of reversible phosphorylation include ubiquitin ligases, guanine nucleotide exchange factors, and at least 46 different transcriptional regulators. The dynamic phosphoproteome provides a missing link in a global, integrative view of cellular regulation.
Topics: Binding Sites; Databases, Factual; Epidermal Growth Factor; HeLa Cells; Humans; Kinetics; Mass Spectrometry; Neoplasm Proteins; Peptides; Phosphorylation; Phosphotyrosine; Protein Binding; Protein Processing, Post-Translational; Proteome; Signal Transduction
PubMed: 17081983
DOI: 10.1016/j.cell.2006.09.026 -
PloS One 2019Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF...
BACKGROUND & OBJECTIVE
Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations.
METHODS
Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology.
RESULTS
Serum EGF was inversely correlated with age (r = -0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF.
CONCLUSIONS
This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.
Topics: Adolescent; Adult; Age Factors; Child; Creatinine; Epidermal Growth Factor; Female; Healthy Volunteers; Humans; Magnesium; Male; Sex Factors
PubMed: 30677083
DOI: 10.1371/journal.pone.0211212 -
The Journal of Pediatrics Feb 2010Maternal milk is a complex fluid, with multifunctional roles within the developing gastrointestinal tract. Epidermal growth factor (EGF) and heparin-binding EGF-like... (Review)
Review
Maternal milk is a complex fluid, with multifunctional roles within the developing gastrointestinal tract. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) are members of the family of EGF-related peptides. Biological actions of these growth factors are mediated via interaction with the EGF-receptor (EGF-R). In the early postnatal period, breast milk is the major source of EGF for the developing intestinal mucosa. HB-EGF is also detected in breast milk, but in concentrations 2 to 3 times lower than EGF. With normal physiological conditions, the intestinal epithelium undergoes a continuing process of cell proliferation, differentiation, and maturation. EGF plays an important role in these processes. In pathophysiologic situations, EGF contributes to epithelial protection from injury and post-injury mucosal repair. Necrotizing enterocolitis (NEC) is a devastating disease affecting infants born prematurely. The pathogenesis of NEC is not known, and there is no effective treatment for this disease. In an experimental NEC model, oral administration of a physiological dose of EGF significantly reduces the incidence and severity of NEC. HB-EGF provides similar protection against NEC, but only when pharmacological doses are used. Further studies are necessary before EGF can be introduced as an efficient therapeutic approach of intestinal injury.
Topics: Animals; Enterocolitis, Necrotizing; Epidermal Growth Factor; Female; Gastrointestinal Tract; Heparin-binding EGF-like Growth Factor; Humans; Infant; Infant, Newborn; Intercellular Signaling Peptides and Proteins; Intestinal Mucosa; Milk, Human
PubMed: 20105663
DOI: 10.1016/j.jpeds.2009.11.018 -
Acta Cirurgica Brasileira 2023Bone repair aims to restore the anatomical, biomechanical, and functional integrity of the affected structure. Here we study the effects of ascorbic acid (AA) and...
PURPOSE
Bone repair aims to restore the anatomical, biomechanical, and functional integrity of the affected structure. Here we study the effects of ascorbic acid (AA) and epidermal growth factor (EGF) applied in a single dose and in combination on the repair of a noncritical bone defect model.
METHODS
Twenty-four rats were divided into four groups: an intact G-1 control group, and three groups that underwent a noncritical bone defect in the right tibia: G-2 treated with AA, G-3 treated with EGF, and G-4 treated with AA in combination with EGF. After 21 days of treatment, rats were sacrificed, the tibias were dissected and a destructive biomechanical analysis of three-point flexion test was performed in a universal testing machine; the values of stiffness, resistance, maximum energy, and energy at maximum load were statistically compared.
RESULTS
G-3 and G-4 recovered the biomechanical properties of strength and stiffness of an intact tibia 3 weeks after their application. Not so the energy and energy at maximum load. For G-2, only the stiffness of an intact tibia was recovered.
CONCLUSIONS
EGF and AA-EGF applied to a noncritical bone defect in the rat tibia favors the recovery of bone resistance and stiffness.
Topics: Rats; Animals; Tibia; Epidermal Growth Factor; Ascorbic Acid; Biomechanical Phenomena
PubMed: 37132758
DOI: 10.1590/acb381623 -
The Journal of Investigative Dermatology Jul 1993Hair follicles arise in developing skin as a result of a complex of interactions that are likely to be mediated by diffusible, cell- and matrix-bound factors. Growth... (Review)
Review
Hair follicles arise in developing skin as a result of a complex of interactions that are likely to be mediated by diffusible, cell- and matrix-bound factors. Growth factors such as fibroblast growth factor (FGF) and epidermal growth factor (EGF) have been implicated in the control of epidermal and mesenchymal cell function, and it is likely that they also affect proliferation and differentiation of the cells of the cutaneous appendages during development. Immunolocalization of basic FGF adjacent to areas of proliferation in developing and in mature follicles suggests that this factor may regulate the mitotic activity of epithelially-derived cells; acidic FGF, on the other hand, appears in the differentiating cells of the follicle bulb and may therefore participate in the formation of structural components of the follicle or of the fiber. EGF has been identified as a potent modulator of cellular growth and is also present during follicle differentiation. These factors may act through autocrine and paracrine mechanisms because their receptors are also found on epidermally derived and mesenchymal structures in the skin. We have studied the effects of these growth factors on hair follicle development in the newborn mouse. Daily injections for 1 week after birth resulted in significant changes in the morphogenesis of the hair follicle population. Histologic examination of skin of FGF-treated mice suggested that the growth factor had affected hair follicle initiation and development, which resulted in a significant delay in the first and subsequent hair cycles when compared to control animals. Because aFGF and bFGF are not readily diffusible, these effects remained confined to the area of treatment. In contrast, EGF affected the whole body coat of the treated animals, induced hyperkeratinization of the skin, and caused a significant delay in hair follicle development.
Topics: Animals; Epidermal Growth Factor; Fibroblast Growth Factors; Hair; Mice
PubMed: 8326142
DOI: 10.1111/1523-1747.ep12363020 -
International Journal of Molecular... Aug 2023Re-epithelialization is delayed in aged skin due to a slow rate of keratinocyte proliferation, and this may cause complications. Thus, there has been development of new...
Re-epithelialization is delayed in aged skin due to a slow rate of keratinocyte proliferation, and this may cause complications. Thus, there has been development of new therapies that increase treatment efficacy for skin wounds. Epidermal growth factor (EGF) has been clinically used, but this agent is expensive, and its activity is less stable. Therefore, a stable compound possessing EGF-like properties may be an effective therapy, especially when combined with EGF. The current study discovered that pinocembrin (PC) effectively synergized with EGF in increasing keratinocyte viability. The combination of PC and EGF significantly enhanced the proliferation and wound closure rate of the keratinocyte monolayer through activating the phosphorylation of ERK and Akt. Although these effects of PC were like those of EGF, we clearly proved that PC did not transactivate EGFR. Recent data from a previous study revealed that PC activates G-protein-coupled receptor 120 which further activates ERK1/2 and Akt phosphorylation. Therefore, this clearly indicates that PC possesses a unique property to stimulate the growth and survival of keratinocytes through activating a different receptor, which subsequently conveys the signal to cross-talk with the effector kinases downstream of the EGFR, suggesting that PC is a potential compound to be combined with EGF.
Topics: Humans; Aged; Epidermal Growth Factor; ErbB Receptors; Proto-Oncogene Proteins c-akt; Keratinocytes; Phosphorylation; Cell Proliferation
PubMed: 37569825
DOI: 10.3390/ijms241512450 -
Seminars in Reproductive Medicine Jan 2009The growth and maturation of the ovarian follicle requires the coordinate function of somatic cells and the oocyte. Over the past three decades, numerous growth factors... (Review)
Review
The growth and maturation of the ovarian follicle requires the coordinate function of somatic cells and the oocyte. Over the past three decades, numerous growth factors involved in the bidirectional signals between the somatic and germ cells have been identified. A possible function of epidermal growth factor (EGF) signaling at selected stages of follicle maturation had been proposed early on and is supported by many observations of in vitro effects of this growth factor on steroidogenesis, oocyte maturation, and cumulus expansion. However, attempts to link EGF levels in the follicular fluid with the state of follicle and oocyte maturation have been inconclusive. More recently, data generated using mouse genetic models perturbing ovulation and fertility indicate that EGF-like growth factors, rather than EGF itself, accumulate in the follicle at the time of ovulation. EGF-like growth factor mRNA is regulated by the luteinizing hormone surge, and corresponding proteins are detected in the follicle. The EGF-like growth factors amphiregulin, epiregulin, and betacellulin are potent stimulators of oocyte maturation and cumulus expansion, and perturbation of this EGF network in vivo impairs ovulation. Similar findings in species other than the mouse confirm an important physiological role for this network at the time of ovulation. Whether this network also plays a critical role in humans and whether it can be used as a biological marker of follicle development or for the improvement of fertility remains to be determined. This review summarizes the most recent findings on the EGF network during ovulation and the potential clinical applications of manipulating this intercellular communication pathway in the control of fertility.
Topics: Animals; Cell Proliferation; Cumulus Cells; Epidermal Growth Factor; Female; Follicular Fluid; Humans; Intercellular Signaling Peptides and Proteins; Models, Biological; Oocytes; Oogenesis; Ovulation; Transforming Growth Factor alpha
PubMed: 19197805
DOI: 10.1055/s-0028-1108010 -
International Wound Journal Aug 2023Epidermal growth factor (EGF) is a growth factor that plays a pivotal role in wound healing and maintaining tissue homeostasis by regulating cell survival,... (Review)
Review
Epidermal growth factor (EGF) is a growth factor that plays a pivotal role in wound healing and maintaining tissue homeostasis by regulating cell survival, proliferation, migration, and differentiation. Exogenous administration of bioidentical human recombinant epidermal growth factor (rhEGF) has been known to promote skin wound healing, although rhEGF is increasingly being used in drug delivery systems and nanotechnology. However, despite considerable attention being focused on the potential clinical applications of rhEGF in several dermatological conditions beyond wound healing, the number of studies still remains relatively low. Herein, we conducted a literature search of PubMed/Medline and Google Scholar databases to retrieve published literature related to rhEGF and summarised the effects of rhEGF in the treatment of various wound types, radiotherapy or chemotherapy-related skin reactions, atopic dermatitis, skin aging, and post-inflammatory hyperpigmentation.
Topics: Humans; Epidermal Growth Factor; Recombinant Proteins; Wound Healing; Drug Delivery Systems
PubMed: 36584669
DOI: 10.1111/iwj.14075 -
FASEB Journal : Official Publication of... May 2022Epidermal growth factor (EGF) is produced in the kidney by thick ascending limbs of the loop of Henle and by distal convoluted tubules (DCTs). Reduced urinary EGF levels...
Epidermal growth factor (EGF) is produced in the kidney by thick ascending limbs of the loop of Henle and by distal convoluted tubules (DCTs). Reduced urinary EGF levels have been associated with chronic kidney disease but it is not known whether physiological levels of EGF protect the kidney from progressive renal disease. Here, we show that EGF-deficient mice on a mixed genetic background had increased urinary microalbumin, and a subset of these mice developed severe progressive renal disease with azotemia that was not seen in WT or TGFα-deficient littermates with this mixed genetic background. These azotemic EGF-deficient mice developed crescentic glomerulonephritis linked to HB-EGF/EGFR hyperactivation in glomeruli, as well as attenuation of the proximal tubule brush border, distal convoluted tubule (DCT) dilatation, and kidney fibrosis associated with renal β-catenin/mTOR hyperactivation. The observation of these severe renal pathologies only in a subset of EGF-deficient mice suggests that independent segregation of strain-specific modifier alleles contributes to the severity of the renal abnormalities that only manifest when EGF is lacking. These findings link the lack of EGF to renal pathologies in the adult mammalian kidney, in support of a role of physiological levels of EGF for maintaining the function of glomeruli, proximal tubules, and DCTs. These observations suggest that diminished EGF levels predispose kidneys to progressive renal disease.
Topics: Acute Kidney Injury; Animals; Epidermal Growth Factor; Female; Humans; Kidney; Kidney Glomerulus; Kidney Tubules, Distal; Kidney Tubules, Proximal; Male; Mammals; Mice
PubMed: 35442545
DOI: 10.1096/fj.202101837R -
Seminars in Cell & Developmental Biology Apr 2014In 1962, epidermal growth factor (EGF) was discovered by Dr. Stanley Cohen while studying nerve growth factor (NGF). It was soon recognized that EGF is the prototypical... (Review)
Review
In 1962, epidermal growth factor (EGF) was discovered by Dr. Stanley Cohen while studying nerve growth factor (NGF). It was soon recognized that EGF is the prototypical member of a family of peptide growth factors that activate the EGF receptors, and that the EGF/EGF receptor signaling pathway plays important roles in proliferation, differentiation and migration of a variety of cell types, especially in epithelial cells. After the basic characterization of EGF function in the first decade or so after its discovery, the studies related to EGF and its signaling pathway have extended to a broad range of investigations concerning its biological and pathophysiological roles in development and in human diseases. In this review, we briefly describe the gene organization and tissue distribution of EGF, with emphasis on its biological and pathological roles in human diseases.
Topics: Animals; Cell Differentiation; Epidermal Growth Factor; Epithelial Cells; ErbB Receptors; Gene Expression; Humans; Signal Transduction
PubMed: 24513230
DOI: 10.1016/j.semcdb.2014.01.011