ArticleThe Journal of cell biology2003
Essential functions of p21-activated kinase 1 in morphogenesis and differentiation of mammary glands.
Article in The Journal of cell biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity.Biomedicines · 2023Review
- PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediatedInternational journal of biological sciences · 2023Article
- Novel biomarkers and prediction model for the pathological complete response to neoadjuvant treatment of triple-negative breast cancer.Journal of Cancer · 2021Article
- Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.Cancer metastasis reviews · 2020Review
- Scribble promotes alveologenesis in the pregnant mammary gland for milk production.Reproduction (Cambridge, England) · 2020Article
- Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion.Scientific reports · 2019Article
- Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication.Frontiers in oncology · 2019Review
- Signaling coupled epigenomic regulation of gene expression.Oncogene · 2017Review
- A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.Molecular therapy. Nucleic acids · 2017Article
- An anti-cancer WxxxE-containing azurin polypeptide inhibits Rac1-dependent STAT3 and ERK/GSK-3β signaling in breast cancer cells.Oncotarget · 2017Article
- STAT5A/5B-specific expansion and transformation of hematopoietic stem cells.Blood cancer journal · 2017Article
- Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study.Acta oncologica (Stockholm, Sweden) · 2016Article
- Minireview: Mouse Models of Rho GTPase Function in Mammary Gland Development, Tumorigenesis, and Metastasis.Molecular endocrinology (Baltimore, Md.) · 2016Review
- Differential mRNA expression levels of human histone-modifying enzymes in normal karyotype B cell pediatric acute lymphoblastic leukemia.International journal of molecular sciences · 2013Article
- Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways.Genes & development · 2012Article
- PAK signaling in cancer.Cellular logistics · 2012Article
- Dynamics of the G protein-coupled vasopressin V2 receptor signaling network revealed by quantitative phosphoproteomics.Molecular & cellular proteomics : MCP · 2012Article
- Signal transducer and activator of transcription 5 as a key signaling pathway in normal mammary gland developmental biology and breast cancer.Breast cancer research : BCR · 2011Review
- PAK1 as a therapeutic target.Expert opinion on therapeutic targets · 2010Review
- PAK signaling in oncogenesis.Oncogene · 2009Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Although growth factors have been shown to influence mammary gland development, the nature of downstream effectors remains elusive. In this study, we show that the expression of p21-activated kinase (Pak)1, a serine/threonine protein kinase, is activated in mammary glands during pregnancy and lactation. By targeting an ectopic expression of a kinase-dead Pak1 mutant under the control of ovine beta-lactoglobulin promoter, we found that the mammary glands of female mice expressing kinase-dead Pak1 transgene revealed incomplete lobuloalveolar development and impaired functional differentiation. The expression of whey acidic protein and beta-casein and the amount of activated Stat5 in the nuclei of epithelial cells in transgenic mice were drastically reduced. Further analysis of the underlying mechanisms revealed that Pak1 stimulated beta-casein promoter activity in normal mouse mammary epithelial cells and also cooperated with Stat5a. Pak1 directly interacted with and phosphorylated Stat5a at Ser 779, and both COOH-terminal deletion containing Ser 779 of Stat5a and the Ser 779 to Ala mutation completely prevented the ability of Pak1 to stimulate beta-casein promoter. Mammary glands expressing inactive Pak1 exhibited a reduction of Stat5a Ser 779 phosphorylation. These findings suggest that Pak1 is required for alveolar morphogenesis and lactation function, and thus, identify novel functions of Pak1 in the mammary gland development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.