Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 5 of 5

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Muc4 Modulation Of Ligand-Independent Erbb2 Signaling, Goldi Attias Kozloski May 2011

Muc4 Modulation Of Ligand-Independent Erbb2 Signaling, Goldi Attias Kozloski

Goldi A Kozloski

The membrane mucin Muc4 is a heterodimer, bi-functional glycoprotein complex that is normally expressed in epithelial tissue. Functional studies on the extracellular mucin subunit of Muc4 have shown that it acts to promote anti-adhesion properties by sterically interfering with cell-cell and cell-matrix interactions and that the extent of this effect is directly associated with the number of tandem repeats on this subunit. Functional studies on the transmembrane subunit of Muc4 have shown that this subunit participates in intracellular signaling through interaction with the receptor tyrosine kinase ErbB2. This role of Muc4 was shown to be mediated by stabilizing the heregulin ...


Micrornas Are Independent Predictors Of Outcome In Diffuse Large B-Cell Lymphoma Patients Treated With R-Chop, Goldi Kozloski Apr 2011

Micrornas Are Independent Predictors Of Outcome In Diffuse Large B-Cell Lymphoma Patients Treated With R-Chop, Goldi Kozloski

Goldi A Kozloski

PURPOSE:
Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power.
EXPERIMENTAL DESIGN:
We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to ...


Mechanistic And Signaling Analysis Of Muc4-Erbb2 Signaling Module: New Insights Into The Mechanism Of Ligand-Independent Erbb2 Activity, Goldi Kozloski Sep 2010

Mechanistic And Signaling Analysis Of Muc4-Erbb2 Signaling Module: New Insights Into The Mechanism Of Ligand-Independent Erbb2 Activity, Goldi Kozloski

Goldi A Kozloski

The membrane mucin Muc4 is aberrantly expressed in numerous epithelial carcinomas and is currently used as a cancer diagnostic and prognostic tool. Muc4 can also potentiate signal transduction by modulating differential ErbB2 phosphorylation in the absence and in the presence of the ErbB3 soluble ligand heregulin (HRG-beta1). These features of Muc4 suggest that Muc4 is not merely a cancer marker, but an oncogenic factor with a unique-binding/activation relationship with the receptor ErbB2. In the present study, we examined the signaling mechanisms that are associated with the Muc4-ErbB2 module by analyzing ErbB2 differential signaling in response to Muc4 expression. Our ...


Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski Dec 2009

Muc4/Muc4 Functions And Regulation In Cancer., Goldi Kozloski

Goldi A Kozloski

The membrane mucin MUC4 (human) is abundantly expressed in many epithelia, where it is proposed to play a protective role, and is overexpressed in some epithelial tumors. Studies on the rat homologue, Muc4, indicate that it acts through anti-adhesive or signaling mechanisms. In particular, Muc4/MUC4 can serve as a ligand/modulator of the receptor tyrosine kinase ErbB2, regulating its phosphorylation and the phosphorylation of its partner ErbB3, with or without the involvement of the ErbB3 ligand neuregulin. Muc4/MUC4 can also modulate cell apoptosis via multiple mechanisms, both ErbB2 dependent and independent. Muc4/MUC4 expression is regulated by multiple ...


Conformational Changes In Receptor Tyrosine Kinase Signaling: An Erbb Garden Of Delights., Goldi Kozloski Sep 2009

Conformational Changes In Receptor Tyrosine Kinase Signaling: An Erbb Garden Of Delights., Goldi Kozloski

Goldi A Kozloski

The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors.