PDGF C Is A Selective α Platelet-Derived Growth Factor Receptor Agonist That Is Highly Expressed in Platelet α Granules and Vascular Smooth Muscle

  • Li Fang
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Yibing Yan
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Laszlo G. Komuves
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Shirlee Yonkovich
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Carol M. Sullivan
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Bradley Stringer
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Sarah Galbraith
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Nathalie A. Lokker
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • S. Stuart Hwang
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Paquita Nurden
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • David R. Phillips
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.
  • Neill A. Giese
    From Millennium Pharmaceuticals (L.F., Y.Y., L.G.K., S.Y., C.M.S., N.A.L., S.S.H., D.R.P., N.A.G.), South San Francisco, Calif; Millennium Pharmaceuticals (B.S., S.G.), Cambridge, Mass; and Laboratoire d’Hématologie (P.N.), Hôpital Cardiologique, Pessac, France.

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<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> 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 α and β PDGF receptor (PDGFR) tyrosine kinases. This study was performed to determine the receptor specificity and cellular expression profile of PDGF C. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> PDGF C growth factor domain (GFD) was shown to preferentially bind and activate α PDGFR and activate β PDGFR when it is co-expressed with α 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 α 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> 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. </jats:p>

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