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 Muschler

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3683-3692
Number of pages10
JournalJournal of Cell Science
Volume123
Issue number21
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

STAT5 Transcription Factor
Dystroglycans
Hormones
Laminin
Basement Membrane
Null Lymphocytes
Human Mammary Glands
Lactation
Prolactin
Growth Hormone

Keywords

  • Dystroglycan
  • Epithelial
  • Growth hormone
  • Laminin
  • Mammary
  • Prolactin
  • STAT5

ASJC Scopus subject areas

  • Cell Biology

Cite this

Leonoudakis, D., Singh, M., Mohajer, R., Mohajer, P., Fata, J. E., Campbell, K. P., & Muschler, J. (2010). Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. Journal of Cell Science, 123(21), 3683-3692. https://doi.org/10.1242/jcs.070680

Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. / Leonoudakis, Dmitri; Singh, Manisha; Mohajer, Roozbeh; Mohajer, Pouya; Fata, Jimmie E.; Campbell, Kevin P.; Muschler, John.

In: Journal of Cell Science, Vol. 123, No. 21, 01.11.2010, p. 3683-3692.

Research output: Contribution to journalArticle

Leonoudakis, D, Singh, M, Mohajer, R, Mohajer, P, Fata, JE, Campbell, KP & Muschler, J 2010, 'Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity', Journal of Cell Science, vol. 123, no. 21, pp. 3683-3692. https://doi.org/10.1242/jcs.070680
Leonoudakis D, Singh M, Mohajer R, Mohajer P, Fata JE, Campbell KP et al. Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. Journal of Cell Science. 2010 Nov 1;123(21):3683-3692. https://doi.org/10.1242/jcs.070680
Leonoudakis, Dmitri ; Singh, Manisha ; Mohajer, Roozbeh ; Mohajer, Pouya ; Fata, Jimmie E. ; Campbell, Kevin P. ; Muschler, John. / Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity. In: Journal of Cell Science. 2010 ; Vol. 123, No. 21. pp. 3683-3692.
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