The tyrosine phosphatase HD-PTP is regulated by FGF-2 through proteasome degradation.
Angiogenesis is essential in development and wound healing and contributes to the pathogenesis of many diseases. The signalling pathways activated in angiogenesis are, in part ,known and the overall tyrosine phosphorylation of cellular proteins plays a relevant role. By RNA fingerprinting, we isolated a tyrosine phosphatase, HD-PTP, modulated in human endothelial cells exposed to human immunodeficiency virus type 1 Tat, a viral protein known to be angiogenic. For the first time, we describe HD-PTP at the protein level. HD-PTP, a 185 kDa cytosolic protein which is expressed in endothelial cells of different origin. We show that HD-PTP is upregulated by Tat at the mRNA but not at the protein level. HD-PTP protein is differentially modulated by two angiogenic growth factors. While Vascular Endothelial Growth Factor does not affect protein levels, Fibroblast Growth Factor-2 induces HD-PTP degradation via the proteasome system.
Mariotti
Massimo
M
Department of Preclinical Sciences, University of Milan Medical School, Via GB Grassi, 74 Milan, Italy. massimo.mariotti@unimi.it
Castiglioni
Sara
S
Beguinot
Laura
L
Maier
Jeanette A M
JA
D018929:Cell Culture Techniques; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016172:DNA Fingerprinting; D015536:Down-Regulation; D042783:Endothelial Cells; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D020869:Gene Expression Profiling; D015696:Gene Products, tat / Q000502:physiology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000502:physiology; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D012333:RNA, Messenger; D014470:Umbilical Cord / Q000098:blood supply; D015854:Up-Regulation
D015853:Cysteine Proteinase Inhibitors; D015696:Gene Products, tat; D007976:Leupeptins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C114102:PTPN23 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde