The VEGF gene is comprised of eight exons separated by seven introns (Figure 1). Exons one through five and eight are common to all isoforms. The first five exons encode for domains involved in a-helical dimerization, a signal peptide cleaved following secretion (exons 1 and 2), and sites for
VEGFR1 (exon 3) and VEGFR2 (exon 4) binding (Robinson and Stringer, 2001). VEGF is alternatively spliced to produce several isoforms that vary in amino acid number in all species studied to date (Table I). Variability among the isoforms results from the inclusion of exons six and/or seven (Figure 1).
The most abundant human isoform in most tissues is VEGF165, and as a result, the most is known about this isoform. There have been several studies of VEGF145 and VEGF121, but few have focused on VEGF189 or VEGF206 because of their low abundance and reported difficulties producing them in pure form. Many of the studies described in the following sections have utilized recombinant human VEGF121 or VEGF 165, whereas studies of VEGF 189 or VEGF206 have utilized in vitro-produced extracellular matrix (ECM), to which these isoforms are bound.
Several additional VEGF isoforms have been described, including murine VEGF115 (Robinson and Stringer, 2001), expressed in immortalized fibroblasts, with 37 novel car-boxy l-terminal amino acids relative to VEGF 120. Human VEGF183 uses an alternative splice donor site 18 nucleotides upstream of the common splice site between exons 6a and 6b, which results in six less amino acids than VEGF189 . Other isoforms have been reported, including VEGF 162 with angiogenic activity, VEGF 165b that may negatively regulate VEGF 165, and VEGF148 with unknown biological activity. The significance of these isoforms awaits further investigation.
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.