title: PDGF C is a selective alpha platelet-derived growth factor receptor agonist that is highly expressed in platelet alpha granules and vascular smooth muscle.
abstract: 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.
authors.affiliation: Millennium Pharmaceuticals, South San Francisco, Calif 94080, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yan
authors.forename: Laszlo G
authors.initials: LG
authors.lastname: Komuves
authors.forename: Shirlee
authors.initials: S
authors.lastname: Yonkovich
authors.forename: Carol M
authors.initials: CM
authors.lastname: Sullivan
authors.forename: Bradley
authors.initials: B
authors.lastname: Stringer
authors.forename: Sarah
authors.initials: S
authors.lastname: Galbraith
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Lokker
authors.forename: S Stuart
authors.initials: SS
authors.lastname: Hwang
authors.forename: Paquita
authors.initials: P
authors.lastname: Nurden
authors.forename: David R
authors.initials: DR
authors.lastname: Phillips
authors.forename: Neill A
authors.initials: NA
authors.lastname: Giese
mesh_terms: 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
chemical_list: 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