[Todos] Seminario IFIBYNE, Lunes 30 de Octubre

[Dana Felman]

Seminario IFIBYNE
(Instituto de Fisiología, Biología Molecular y Neurociencias, UBA-CONICET)

Lunes 30 de octubre 11 hs.
Aula del LFBM.

SPEAKER:
Dr. Kermit Carraway.
University of Miami
School of Medicine

TITLE:
Functions of Muc4, the intramembrane ErbB2 ligand, in epithelial and
tumor cells

ABSTRACT:

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.

--
OMAR ADRIAN COSO Ph.D.
Laboratorio de Fisiologia y Biologia Molecular.
Facultad de Ciencias Exactas y Naturales.
Universidad de Buenos Aires.

Address:
LFBM. Ciudad Universitaria.
Pabellon II. Piso 2.
1428 Buenos Aires
ARGENTINA

Phone: 54-11-4-576-3368/3386.
Fax: 54-11-4-576-3321.
Dr. Osvaldo D. Uchitel
Director
Laboratorio de Fisiología y Biología Molecular
Instituto de Fisiología, Biología Molecular y Neurociencias
CONICET
Facultad de Ciencias Exactas y Naturales, Univ. de Buenos Aires
Pabellon II piso 2
Ciudad Universitaria , Buenos Aires 1428
ARGENTINA

Telephone : ++54 11 4 576 3386 o 3368.
FAX : ++54 11 4 576 3321
NEW MAIL : odu en fbmc.fcen.uba.ar
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