Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tyrosine kinase c-src associates with growth factor receptors, focal contacts and cytoskeletal proteins and is involved in signaling events. The aim of this study was to investigate the role of src in the regulation of mesangial cell (MC) proliferation and differentiation in three-dimensional (3D) culture in collagen gels. Using retroviral gene transfer we have overexpressed wild-type c-src, a kinase-negative c-src mutant (c-src295) and transforming v-src in MC. The MC differentiation in 3D culture was characterized by the formation of a nonproliferating multicellular network in control cells and in cells expressing wild-type c-src. Immunoblotting demonstrated a rapid down-regulation of the alpha-smooth muscle actin expression. The kinase-negative MC (c-src295) failed to differentiate, maintained a significant proliferative rate, and the alpha-smooth muscle actin expression remained stable during 3D culture. MC transformed with v-src showed a high level of tyrosine phosphorylation and proliferation in 3D culture. Analyses of proteins involved in cell cycle regulation demonstrated dephosphorylation of the retinoblastoma protein (Rb) during 3D culture in control and c-src transfected cells. Expression of v-src resulted in sustained Rb phosphorylation. Zymographic analysis of plasminogen activator (u-PA) revealed an inhibition of u-PA secretion in MC transfected with c-src295. These results indicate that c-src exerts regulatory effects on MC proliferation, cytoskeletal organization, matrix proteases and differentiation. Targeted manipulation of the c-src kinase may be useful in modulating MC behavior in vivo.
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PMID:pp60c-src is required for the induction of a quiescent mesangial cell phenotype. 899 24

Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells. This study was designed to reveal a receptor involved in the biological activities of PEDF. Using a yeast two-hybrid screening, we identified a novel gene from pigment epithelium of the human retina that codes for a PEDF-binding partner, which we term PEDF-R. The derived polypeptide has putative transmembrane, intracellular and extracellular regions, and a phospholipase domain. Recently, PEDF-R (TTS-2.2/independent phospholipase A(2) (PLA(2))zeta and mouse desnutrin/ATGL) has been described in adipose cells as a member of the new calcium-independent PLA(2)/nutrin/patatin-like phospholipase domain-containing 2 (PNPLA2) family that possesses triglyceride lipase and acylglycerol transacylase activities. Here we describe the PEDF-R gene expression in the retina and its heterologous expression by bacterial and eukaryotic systems, and we demonstrate that its protein product has specific and high binding affinity for PEDF, has a potent phospholipase A(2) activity that liberates fatty acids, and is associated with eukaryotic cell membranes. Most importantly, PEDF binding stimulates the enzymatic phospholipase A(2) activity of PEDF-R. In conclusion, we have identified a novel PEDF-R gene in the retina for a phospholipase-linked membrane protein with high affinity for PEDF, suggesting a molecular pathway by which ligand/receptor interaction on the cell surface could generate a cellular signal.
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PMID:Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. 1703 52