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| Figure 1. Receptor-ligand interactions of the PDGF family members. [Note: figure adapted from Li, X. & U. Eriksson (2003) Cytokine Growth Factor Rev. 14:91.] |
The four PDGF isoforms (A, B, C, and D) are characterized by a highly conserved eight-cysteine domain termed the PDGF/VEGF homology domain. The PDGF isoforms exist as disulfide-linked homo- and heterodimers and differentially bind homo- and heterodimer combinations of two receptor tyrosine kinases, PDGF Rα and PDGF Rß (Figure 1).
PDGF-AA
Widely expressed in fibroblasts, osteoblasts, platelets, macrophages, smooth muscle cells, endothelial cells, and Langerhans cells, PDGF-AA activity is ubiquitous, but dependent on cell expression of PDGF Rα. PDGF-AA plays key roles in protein synthesis, chemotaxis inhibition, embryonic neuron fiber development, and bronchial lung development.
PDGF-AB
PDGF-AB demonstrates mitogenic activity for vascular smooth muscle cells as well as stimulating angiogenesis in the heart. Parallel to PDGF-AA and PDGF-BB expression, PDGF-AB is important in a wide variety of cellular processes of the immune, nervous, and cardiovascular systems.
PDGF-BB
Mainly expressed in endothelial cells, PDGF-BB participates in angiogenesis and arterialization of early organ, respiratory, and neuronal development. PDGF-BB is also observed in platelets, neurons, macrophages, and fetal fibroblasts. PDGF-BB, via PDGF Rß, is involved in cellular proliferation and transforming growth factor-like activities.
PDGF-CC
PDGF-CC and -DD form a novel subgroup of the PDGF family distinguished by structural differences that include an N-terminal CUB domain. Widely expressed in multiple embryonic and adult cell, tissue, and organ types, PDGF-CC appears to be important for angiogenesis, cardiovasculature development, and tumorigenesis.
PDGF-DD
The fairly restricted expression pattern of PDGF-DD, compared to other family members, suggests a highly specific function yet to be elucidated. PDGF-DD is co-expressed at lower levels with other family members in the heart, lung, kidney, and musculature and it has been implicated in cardiovasculature development, tumorigenesis, and tissue regeneration.
PDGF-Receptors:
PDGF Rα & PDGF Rß
PDGF Ra and PDGF Rß contain five immunoglobulin-like extracellular domains and an intracellular split tyrosine kinase domain. PDGF receptors are independently regulated in fibroblasts, osteoblasts, chondroblasts, smooth muscle, glia, and endothelium. The PDGF receptors function as homo- and/or heterodimers depending on the cell type. Upon receptor ligation, autophosphorylation initiates a variety of signal transduction cascades.