A 70 amino acid region within the semaphorin domain activates specific cellular response of semaphorin family members.
The semaphorin family contains secreted and transmembrane signaling proteins that function in the nervous, immune, and cardiovascular systems. Chick collapsin-1 is a repellent for specific growth cones. Two other secreted members of the semaphorin family, collapsin-2 and -3, are structurally similar to collapsin-1 but have different biological activities. Semaphorins contain a 500 amino acid family signature semaphorin domain. We show in this study that (1) the semaphorin domain of collapsin-1 is both necessary and sufficient for biological activity, (2) the semaphorin domain contains a 70 amino acid region that specifies the biological activity of the three family members, and (3) the positively charged carboxy terminus potentiates activity without affecting specificity. We propose that semaphorins interact with their receptors through two independent binding sites: one that mediates the biological response and one that potentiates it.
Koppel
A M
AM
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Feiner
L
L
Kobayashi
H
H
Raper
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D017124:Conserved Sequence; D015870:Gene Expression; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039942:Neuropilin-1; D010957:Plasmids; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D040121:Semaphorin-3A; D012680:Sensitivity and Specificity
D030161:Avian Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C094536:SEMA3D protein, Gallus gallus; D040121:Semaphorin-3A; D039942:Neuropilin-1