 |
| 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. |