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

Autor: Bradley J. Stringer, László G. Kömüves, Neill A. Giese, S. Stuart Hwang, David R. Phillips, Paquita Nurden, Shirlee Yonkovich, Nathalie Lokker, Yibing Yan, Li Fang, Sarah Galbraith, Carol M. Sullivan
Rok vydání: 2004
Předmět:
Blood Platelets
medicine.medical_specialty
DNA
Complementary
Vascular smooth muscle
Platelet-derived growth factor
Recombinant Fusion Proteins
medicine.medical_treatment
Biology
Cytoplasmic Granules
Transfection
Muscle
Smooth
Vascular
Cell Line
Embryonic and Fetal Development
Mice
chemistry.chemical_compound
Internal medicine
Endopeptidases
medicine
Animals
Humans
Receptors
Platelet-Derived Growth Factor
Platelet
RNA
Messenger
Platelet activation
Phosphorylation
Platelet-Derived Growth Factor
Lymphokines
Mice
Inbred BALB C
Growth factor
Skeletal muscle
Proto-Oncogene Proteins c-sis
Platelet Activation
Molecular biology
medicine.anatomical_structure
Endocrinology
chemistry
Organ Specificity
biology.protein
Cardiology and Cardiovascular Medicine
Dimerization
Protein Processing
Post-Translational
Tyrosine kinase
Platelet-derived growth factor receptor
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 24:787-792
ISSN: 1524-4636
1079-5642
DOI: 10.1161/01.atv.0000120785.82268.8b
Popis: 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 α and β PDGF receptor (PDGFR) tyrosine kinases. This study was performed to determine the receptor specificity and cellular expression profile of PDGF C. Methods and Results— 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. 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.
Databáze: OpenAIRE
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