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<br>
<font size=5>Seminario IFIBYNE<br>
(Instituto de Fisiología, Biología Molecular y Neurociencias,
UBA-CONICET)<br>
<br>
Lunes 30 de octubre 11 hs.<br>
Aula del LFBM.<br>
<br>
SPEAKER:<br>
Dr. Kermit Carraway.<br>
University of Miami<br>
School of Medicine<br>
<br>
TITLE:<br>
Functions of Muc4, the intramembrane ErbB2 ligand, in epithelial
and<br>
tumor cells<br>
<br>
ABSTRACT:<br>
<br>
The membrane mucin Muc4 comprises a highly O-glycosylated mucin subunit
linked to the membrane by a transmembrane subunit containing two EGF-like
domains, one of which binds directly to the receptor tyrosine kinase
ErbB2. Association of these two membrane proteins occurs shortly after
they are synthesized. In polarized epithelial cells, the
Muc4-ErbB2complex transits to the apical surface of the cells, thus
segregating the ErbB2 from its favored dimerization partner for cellular
signaling, ErbB3, which is localized to adherens junctions. Muc4-ErbB2
complex formation is associated with limited phosphorylation of the ErbB2
and, in polarized epithelial cells, activation of p38 MAP kinase.
Exogenous neuregulin in nonpolarized cells expressing Muc4 induces a
hyperphosphorylation of both ErbB2 and ErbB3, indicating that Muc4 can
potentiate neuregulin signaling. Muc4 is a potent anti-adhesive, which
can block cadherin-mediated contact inhibition. As an anti-adhesive Muc4
would be expected to trigger anoikis, but instead it acts to repress
apoptosis induced by a number of mechanisms, including cell starvation,
chemotherapeutic drugs and loss of adhesion. Repression of apoptosis
apparently involves at least two different mechanisms, one requiring
neuregulin and ErbB3 and the other through ErbB2 without ErbB3. The
protection of cells from anoikis is associated with Muc4 repression of
ErbB2 degradation. These combined findings indicate that Muc4 may be a
potent contributor to both differentiation and cancer.<br>
<br>
</font><font face="Courier New, Courier">-- <br>
</font>OMAR ADRIAN COSO Ph.D.<br>
Laboratorio de Fisiologia y Biologia Molecular.<br>
Facultad de Ciencias Exactas y Naturales.<br>
Universidad de Buenos Aires.<br>
<br>
Address:<br>
LFBM. Ciudad Universitaria.<br>
Pabellon II. Piso 2.<br>
1428 Buenos Aires<br>
ARGENTINA<br>
<br>
Phone: 54-11-4-576-3368/3386.<br>
Fax: 54-11-4-576-3321.<br>
Dr. Osvaldo D. Uchitel <br>
Director<br>
Laboratorio de Fisiología y Biología Molecular<br>
Instituto de Fisiología, Biología Molecular y Neurociencias<br>
CONICET<br>
Facultad de Ciencias Exactas y Naturales, Univ. de Buenos Aires<br>
Pabellon II piso 2<br>
Ciudad Universitaria , Buenos Aires 1428<br>
ARGENTINA<br>
<br>
Telephone : ++54 11 4 576 3386 o 3368.<br>
FAX : ++54 11 4 576 3321 <br>
NEW MAIL : odu@fbmc.fcen.uba.ar<br>
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