Tài liệu Báo cáo khoa học: Structural and functional specificities of PDGF-C and PDGF-D, the novel

REVIEW ARTICLE

Structural and functional specificities of PDGF-C and

PDGF-D, the novel members of the platelet-derived growth

factors family

Laila J. Reigstad1,2, Jan E. Varhaug2,3 and Johan R. Lillehaug1

1 Department of Molecular Biology, University of Bergen, Norway

2 Department of Surgical Sciences, University of Bergen, Norway

3 Haukeland University Hospital, Bergen, Norway

Introduction

The platelet-derived growth factors PDGF-A and -B

have since the late 1970s been recognized as important

factors regulating embryonic development, differenti￾ation, cell growth and many diseases including malig￾nancies. The PDGFs have been classified as members

of the superfamily of growth factors characterized by

the strongly conserved pattern of six cysteine residues

making up intra- and intermonomer disulfide bridges,

the cystine knot family of proteins [1–3]. Examples of

cystine knot subfamilies are the glycoprotein hormone

family [4], the cyclotide family [5,6], and the TGFb

family and NGF family [2]. Extended information

about subfamilies can be obtained in the Cystine Knot

Database (http://hormone.stanford.edu/cystine-knot).

This review focuses on the structure and function of

the two novel members, PDGF-C and -D, of the

PDGF subfamily of the cystine knot superfamily. The

PDGFs show high sequence identity with the vascular

Keywords

PDGF; cystine knot; CUB; growth factor

domain

Correspondence

J. R. Lillehaug, Department of Molecular

Biology, University of Bergen, Post Box

7800, 5020 Bergen, Norway

Fax: +47 55 58 96 83

Tel: +47 55 58 64 21

E-mail: [email protected]

(Received 15 July 2005, revised 19

September 2005, accepted 22 September

2005)

doi:10.1111/j.1742-4658.2005.04989.x

The platelet-derived growth factor (PDGF) family was for more than

25 years assumed to consist of only PDGF-A and -B. The discovery of the

novel family members PDGF-C and PDGF-D triggered a search for novel

activities and complementary fine tuning between the members of this fam￾ily of growth factors. Since the expansion of the PDGF family, more than

60 publications on the novel PDGF-C and PDGF-D have been presented,

highlighting similarities and differences to the classical PDGFs. In this

paper we review the published data on the PDGF family covering struc￾tural (gene and protein) similarities and differences among all four family

members, with special focus on PDGF-C and PDGF-D expression and

functions. Little information on the protein structures of PDGF-C and -D

is currently available, but the PDGF-C protein may be structurally more

similar to VEGF-A than to PDGF-B. PDGF-C contributes to normal

development of the heart, ear, central nervous system (CNS), and kidney,

while PDGF-D is active in the development of the kidney, eye and brain.

In adults, PDGF-C is active in the kidney and the central nervous system.

PDGF-D also plays a role in the lung and in periodontal mineralization.

PDGF-C is expressed in Ewing family sarcoma and PDGF-D is linked to

lung, prostate and ovarian cancers. Both PDGF-C and -D play a role in

progressive renal disease, glioblastoma ⁄ medulloblastoma and fibrosis in

several organs.

Abbreviations

CNS, central nervous system; CUB, Clr ⁄ Cls, urchin EGF-like protein and bone morphogenic protein 1; CVB3, coxsackievirus B3;

EGF, endothelial growth factor; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor.

FEBS Journal 272 (2005) 5723–5741 ª 2005 The Authors Journal compilation ª 2005 FEBS 5723