PDGF C is a selective alpha platelet-derived growth factor receptor agonist that is highly expressed in platelet alpha granules and vascular smooth muscle.
OBJECTIVE
The platelet-derived growth factor (PDGF) family consists of four members, PDGF A, PDGF B, and 2 new members, PDGF C and PDGF D, which signal through the alpha and beta PDGF receptor (PDGFR) tyrosine kinases. This study was performed to determine the receptor specificity and cellular expression profile of PDGF C.


RESULTS
PDGF C growth factor domain (GFD) was shown to preferentially bind and activate alpha PDGFR and activate beta PDGFR when it is co-expressed with alpha PDGFR through heterodimer formation. An investigation of PDGF C mRNA and protein expression revealed that during mouse fetal development, PDGF C was expressed in the mesonephric mesenchyme, prefusion skeletal muscle, cardiac myoblasts, and in visceral and vascular smooth muscle, whereas in adult human tissues expression was largely restricted to smooth muscle. Microarray analysis of various cell types showed PDGF C expression in vascular smooth muscle cells, renal mesangial cells, and platelets. PDGF C mRNA expression in platelets was confirmed by real-time polymerase chain reaction, and PDGF C protein was localized in alpha granules by immuno-gold electron microscopy. Western blot analysis of platelets identified 55-kDa and 80-kDa PDGF C isoforms that were secreted on platelet activation.


CONCLUSIONS
Taken together, our results demonstrated for the first time to our knowledge that like PDGF A and B, PDGF C is likely to play a role in platelet biology.
Fang
Li
L
Millennium Pharmaceuticals, South San Francisco, Calif 94080, USA.
Yan
Yibing
Y
Komuves
Laszlo G
LG
Yonkovich
Shirlee
S
Sullivan
Carol M
CM
Stringer
Bradley
B
Galbraith
Sarah
S
Lokker
Nathalie A
NA
Hwang
S Stuart
SS
Nurden
Paquita
P
Phillips
David R
DR
Giese
Neill A
NA
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D019281:Dimerization; D005314:Embryonic and Fetal Development; D010450:Endopeptidases / Q000097:blood; D006801:Humans; D008222:Lymphokines; D051379:Mice / Q000196:embryology; D008807:Mice, Inbred BALB C; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009928:Organ Specificity; D010766:Phosphorylation; D015539:Platelet Activation; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D020574:Proto-Oncogene Proteins c-sis / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection
D018076:DNA, Complementary; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C075278:platelet-derived growth factor A; C411423:platelet-derived growth factor C; D017479:Receptors, Platelet-Derived Growth Factor; D010450:Endopeptidases