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General Comment |
Semaphorins, or collapsins, constitute a family characterized by the presence of a conserved semaphorin domain at the N
terminus (see OMIM 601124). To identify proteins responsible for non-multidrug resistance resistance to the
chemotherapeutic agent cisplatin (CDDP), Yamada et al. (1997) introduced a CDDP-resistant human ovarian cancer cell
cDNA expression library into CDDP-sensitive cells and selected for CDDP-resistance. They isolated a cDNA encoding a
predicted protein that has 93% amino acid homology to mouse semaphorin E. The 616-amino acid human semaphorin E
contains an N-terminal signal sequence of 15 amino acids that is followed by a semaphorin domain. In vitro translation of
the semaphorin E cDNA yielded a 70-kD protein. Semaphorins are the lignads for plexins Tamagnone L, et al reviewed signalling by semaphorin receptors: cell guidance and beyond.
Semaphorins are a large family of secreted or cell-bound signals, known to guide
axons in developing nervous tissue. They are expressed in a variety of adult and
embryonic tissues and are thought to have a broader spectrum of functions. Recent
evidence suggests that semaphorins and their receptors play a key role in the control
of cellular interactions, most likely in cell-cell repulsion. A subset of semaphorins
interacts with neuropilins - cell-surface molecules lacking a signalling-competent
cytoplasmic domain. Another large family of transmembrane molecules, namely
plexins, bind specifically to semaphorins. Thus plexins, alone, or in association with
neuropilins, behave as fully functional semaphorin receptors. The intracellular
responses elicited by plexins are unknown, but their large cytoplasmic moiety,
containing the strikingly conserved sex-plexin (SP) domain, is likely to trigger novel
signal-transduction pathways.
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