PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.
Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.
Li
X
X
Ludwig Institute for Cancer Research, Stockholm, Sweden.
Pontén
A
A
Aase
K
K
Karlsson
L
L
Abramsson
A
A
Uutela
M
M
Bäckström
G
G
Hellström
M
M
Boström
H
H
Li
H
H
Soriano
P
P
Betsholtz
C
C
Heldin
C H
CH
Alitalo
K
K
Ostman
A
A
Eriksson
U
U
D000818:Animals; D019556:COS Cells; D010450:Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000737:chemistry / Q000201:enzymology; D015870:Gene Expression / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D007313:Insecta; D007668:Kidney / Q000737:chemistry / Q000196:embryology / Q000201:enzymology; D008024:Ligands; D008222:Lymphokines; D008648:Mesoderm / Q000737:chemistry / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019076:Transgenes / Q000502:physiology
D008024:Ligands; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; C411423:platelet-derived growth factor C; D020796:Receptor, Platelet-Derived Growth Factor alpha; D010450:Endopeptidases