Figure 11.

Model of the pathways required for secretory activation and lactation that are perturbed in Src-/- mice. A) PRLR EXPRESSION. In normal mice PRLR expression increases at parturition, this is absent in the Src-/- mice and they have decreased levels of both PRLR message and protein. B) INTEGRIN CROSSTALK. Integrin-mediated adhesion is essential for STAT5 activation downstream of PRLR signaling and Src may be a required mediator for the β 1 integrin-induced crosstalk. The Src-/- mice have diminished levels of STAT5 phosphorylation. C) POLARITY. Epithelial cell polarity is crucial for secretory activation. The mammary glands of Src-/- mice do not have organized lobuloalveolar structures and many of the epithelial cells do not show restricted apical staining suggesting that Src is required for epithelial cell polarity and organization. D) MILK PROTEIN TRANSCRIPTION. Src-/- mice have significantly less β-casein message compared to wildtype mice. This may be directly related to the decreased levels of STAT5 activation in these cells or Src may also be a required signaling molecule in the additional pathways necessary for milk protein transcription. E) MILK PROTEIN TRANSLATION. Milk protein expression is also regulated at the translational level. Src-/- mice have decreased levels of milk proteins and a possible role for Src in the post-transcriptional regulation has not been investigated.