Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity

Dmitri Leonoudakis; Manisha Singh; Roozbeh Mohajer; Pouya Mohajer; Jimmie E Fata; Kevin P Campbell; John L Muschler

doi:10.1242/jcs.070680

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Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity

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Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity

Dmitri Leonoudakis, Manisha Singh, Roozbeh Mohajer, Pouya Mohajer, Jimmie E Fata, Kevin P Campbell and John L Muschler

Journal of cell science, Vol.123(21), pp.3683-3692

11/01/2010

DOI: 10.1242/jcs.070680

PMCID: PMC2964112

PMID: 20940259

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Abstract

Receptors for basement membrane (BM) proteins, including dystroglycan (DG), coordinate tissue development and function by mechanisms that are only partially defined. To further elucidate these mechanisms, we generated a conditional knockout of DG in the epithelial compartment of the mouse mammary gland. Deletion of DG caused an inhibition of mammary epithelial outgrowth and a failure of lactation. Surprisingly, loss of DG in vivo did not disrupt normal tissue architecture or BM formation, even though cultured Dag1 -null epithelial cells failed to assemble laminin-111 at the cell surface. The absence of DG was, however, associated with a marked loss in activity of signal transducer and activator of transcription 5 (STAT5). Loss of DG perturbed STAT5 signaling induced by either prolactin or growth hormone. We found that DG regulates signaling by both hormones in a manner that is dependent on laminin-111 binding, but independent of the DG cytoplasmic domain, suggesting that it acts via a co-receptor mechanism reliant on DG-mediated laminin assembly. These results demonstrate a requirement for DG in the growth and function of a mammalian epithelial tissue in vivo. Moreover, we reveal a selective role for DG in the control of multiple STAT5-dependent hormone signaling pathways, with implications for numerous diseases in which DG function is compromised.

Dystroglycan

Laminin

Prolactin

STAT5

Mammary

Growth hormone

Epithelial

Details

Title: Subtitle: Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity
Creators: Dmitri Leonoudakis - California Pacific Medical Center Research Institute
Manisha Singh - California Pacific Medical Center Research Institute
Roozbeh Mohajer - California Pacific Medical Center Research Institute
Pouya Mohajer - California Pacific Medical Center Research Institute
Jimmie E Fata - Department of Biology, College of Staten Island, City University of New York
Kevin P Campbell - Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine
John L Muschler - California Pacific Medical Center Research Institute
Resource Type: Journal article
Publication Details: Journal of cell science, Vol.123(21), pp.3683-3692
DOI: 10.1242/jcs.070680
PMID: 20940259
PMCID: PMC2964112
NLM abbreviation: J Cell Sci
ISSN: 0021-9533
eISSN: 1477-9137
Publisher: Company of Biologists
Language: English
Date published: 11/01/2010
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020713702771

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