Protein kinase C-independent activation of mitogen-activated protein kinase by epidermal growth factor in skin fibroblasts. 1996

R Le Panse, and V Mitev, and L M Houdebine, and B Coulomb
INSERM Unité 312, Laboratoire de Dermatologie (Pr. Dubertret), Hôpital Saint Louis, Paris, France.

In this study, we demonstrated that epidermal growth factor (EGF) stimulated the phosphorylation of myelin basic protein (MBP), a mitogen-activated protein kinase (MAPK) substrate, in crude extracts of human dermal fibroblasts. Moreover, using a selective protein kinase C inhibitor, GF 109203X (3-[1-[3-(dimethylamino)propyl]-1 H-indol-3-yl]-4 (1 H-indol-3-yl)-1 H-pyrrole-2,5-dione monohydrochloride), we observed that protein kinase C was partially involved in the total MBP phosphorylation. To determine the role of protein kinase C in the MBP phosphorylation, we separated, using fast protein liquid chromatography, the proteins present in the fibroblast crude extracts; we thus detected two distinct MBP kinase activities. The first one was stimulated by EGF and corresponded to p42mapk and p44mapk isoforms; this stimulation was not modified by GF 109203X. The second MBP kinase activity was not stimulated by EGF and was due to two protein kinase C isoforms reacting with an anti-protein kinase C zeta antibody. These results show that, in human dermal fibroblasts, EGF stimulates p42mapk and p44mapk isoforms in a protein kinase C-independent manner.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008301 Maleimides Derivatives of maleimide (the structural formula H2C2(CO)2NH) containing a pyrroledione ring where the hydrogen atom of the NH group is replaced with aliphatic or aromatic groups.
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D004676 Myelin Basic Protein An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes. Golli-MBP1 Protein,Golli-MBP2 Protein,HOG5 Protein,HOG7 Protein,MBP1 Protein,MBP2 Protein,MBP3 Protein,MBP4 Protein,Myelin Basic Protein, 17.2 kDa Isoform,Myelin Basic Protein, 18.5 kDa Isoform,Myelin Basic Protein, 20.2 kDa Isoform,Myelin Basic Protein, 21.5 kDa Isoform,Myelin Basic Protein, Isoform 1,Myelin Basic Protein, Isoform 2,Myelin Basic Protein, Isoform 3,Myelin Basic Protein, Isoform 4,Myelin Basic Protein, Isoform 5,Myelin Basic Protein, Isoform 6,Myelin Basic Protein, Isoform 7,Golli MBP1 Protein,Golli MBP2 Protein
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone

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