Platelet-derived growth factor and alternative splicing: a review.
The mitogenic and chemotactic potency of platelet-derived growth factor (PDGF) has linked this polypeptide to the pathogenesis of several disease states including atherosclerosis and neoplasia. We have reviewed the recent literature on aspects relating to the structure, distribution and biology of PDGF and its high-affinity cell-surface and intracellular receptors. In addition to platelets, several normal and tumor cells secrete the mitogen in one or more of three possible dimeric configurations. Alternative splicing of exon 6 in PDGF A-chain RNA results in the formation of two protein species with different carboxy-termini. Initially, it was thought that the longer A-chain variant was processed only by transformed cells. However, recent evidence indicates that alternative splicing occurs in several cells which express the A-chain, including early Xenopus embryos. The functional significance of the exon 6 product, a highly basic region spanned by 18 amino acid residues (A194-211), is not precisely clear. We have summarized recent findings which implicate roles for A194-211 in the processing, secretion, and mitogenesis of the A-chain homodimer, nuclear transport signalling, and heparin binding. Thus, alternative splicing could play an important role in the modulation of the functional properties of the PDGF A-chain variants per se and in the complex interactive network of polypeptide growth factors and cytokines.
Khachigian
L M
LM
Department of Haematology, Prince of Wales Hospital, Sydney.
Chesterman
C N
CN
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D005091:Exons / Q000235:genetics / Q000502:physiology; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008934:Mitogens / Q000502:physiology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D006493:Heparin; D017479:Receptors, Platelet-Derived Growth Factor