STAT5A

What is STAT5A protein?

The STAT5A protein, also known as signal transducer and activator of transcription 5A, is a transcription factor involved in mediating the signaling of cytokines and growth factors. It plays a crucial role in various cellular processes such as cell growth, differentiation, and immune response. STAT5A is predominantly expressed in hematopoietic cells and is activated by phosphorylation upon binding of specific ligands to cell surface receptors. Activation of STAT5A leads to its dimerization, nuclear translocation, and binding to specific DNA sequences, resulting in the regulation of target gene expression.

What is the function of STAT5A protein?

Cell proliferation and survival: STAT5A activates genes involved in cell cycle progression and inhibition of apoptosis. This promotes growth and maintenance of cells.

Hematopoiesis: It plays a key role in the development and maintenance of various blood cell lineages like red blood cells, lymphocytes etc. in response to cytokines.

Mammary gland development: STAT5A is crucial for lobuloalveolar maturation and lactation. It regulates milk protein gene expression during pregnancy and lactation.

Immune cell development: It is important for differentiation and functions of multiple immune cell types like T cells, B cells, neutrophils, macrophages etc.

STAT5A related signaling pathway

JAK/STAT pathway: Binding of ligands like Epo, GH or PRL to their receptors leads to JAK kinase activation. JAKs then phosphorylate STAT5A.

PI3K/Akt pathway: STAT5A activation can induce PI3K, resulting in Akt phosphorylation. Akt promotes cell survival.

Ras/Raf/MEK/ERK pathway: STAT5A assists activation of the Ras pathway, regulating gene expression, cell growth and proliferation.

STAT5A Related Diseases

•  Cancer: Constitutively active STAT5A promotes growth and survival in blood cancers like ALL, CML, AML. It's a therapeutic target.
•  Immunodeficiency: Heterozygous mutations in STAT5A cause autosomal dominant hyper-IgE syndrome with immune defects.
•  Primary ovarian insufficiency: STAT5A involvement is implicated in premature menopause and infertility in some cases.
•  Short stature: STAT5A deficiency due to gene deletions causes short stature in both sexes via growth hormone insensitivity.
•  Mammary gland diseases: Abnormal STAT5A levels impact lobuloalveolar development in conditions like mastitis or breast cancer.
•  Cancer therapy: Inhibiting constitutively active STAT5A can treat blood cancers, making it a targeted therapy candidate.
•  Hematopoietic stem cell regulation: Modulating STAT5A levels guides proper HSC self-renewal, differentiation and blood production.
•  Immunotherapy development: STAT5A regulates immune cell development and function, so can be leveraged to enhance vaccine responses.

•  Cancer therapy: Inhibiting constitutively active STAT5A can treat blood cancers, making it a targeted therapy candidate.
•  Hematopoietic stem cell regulation: Modulating STAT5A levels guides proper HSC self-renewal, differentiation and blood production.
•  Immunotherapy development: STAT5A regulates immune cell development and function, so can be leveraged to enhance vaccine responses.