[A short form of the heparin-binding EGF-like growth factor with a changed EGF domain].
In all secreted proteins related to the epidermal growth factor (EGF), EGF domains that occur in a mature factor are each encoded by two exons, and those that do not, by one exon. During splicing, additional exon 3a can be inserted between exons 3 and 4, which code for the EGF domain of the mature heparin-binding EGF-like growth factor (HB-EGF). The resulting mRNA codes for the short form of HB-EGF (SF HB-EGF), which retains the signal peptide, the propeptide, and the heparin-binding domain. However, its EGF domain lacks the C-terminal subdomain essential for the interaction with the EGF receptor (EGFR). Structural analysis suggested that SF HB-EGF is a secreted polypeptide that has high affinity for heparin, but weakly, if at all, interacts with EGFR. Data obtained in three different systems indicated that SF HB-EGF possesses a mitogenic activity but utilizes a signal transduction pathway other than that of HB-EGF.
Luk'ianov
E V
EV
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Viedlokha
A
A
Kuianskaia
D V
DV
Olsnes
S
S
Kozlov
Iu V
IuV
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005091:Exons; D006493:Heparin / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008322:Mammals; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008934:Mitogens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D006493:Heparin; D004247:DNA; D066246:ErbB Receptors