Antibody Panel to STAT Transcription Factors - Product Review 07

Introduction

STATs (signal transducers and activators of transcription) are a family of cytoplasmic latent transcription factors that are activated to regulate gene expression in response to a large number of extracellular signaling polypeptides including cytokines, interferons, and growth factors.

After phosphorylation by JAK tyrosine kinases, STATs enter the nucleus to regulate transcription of many different genes. Among the seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6), STAT1, STAT3, STAT5a, and STAT5b have a wide activation profile.

STAT1 is involved in the TNFR1-TRADD signaling complex. In Hela cells STAT1 acts as a TNFR1-signaling molecule to suppress NF-kB activation. It has also been shown that its activation slows growth and promotes apoptosis. STAT1 deficient knock-out mice are unable to induce IFN regulated genes and are extremely susceptible to viral diseases. After phosphorylation, STAT1 and STAT2 form heterodimers that function as more potent inducers of transcription than the STAT1 homodimer. STAT1 is known to associate with the transcription factors p48, Sp1, and p300.

Human STAT2 cDNA codes for a 851 amino acid protein with a predicted molecular weight of 113 kDa. STAT2 associates with beta subunit of the type I IFN receptor in an interferon-dependent manner. The unique acidic domain of the carboxy-terminal region of STAT2 may interact with cAMP-response-element binding protein.

STAT3 has been shown to be activated by IFN-alpha but not IFN-beta. The transcription factors associated with STAT3 are c-Jun and cyclic AMP-responsive enhancer binding protein (CREB). Deletion of the STAT3 gene in knock-out mice was lethal at the early embryonic stage.

STAT4 is activated when cells are treated with interleukin-12, a key cytokine regulator of cell-mediated immunity. STAT4 is also activated by IFN alpha/beta. In STAT4 knock-out mice, lymphocytes no longer proliferate in response to IL12, produce IFN gamma, or express natural killer cell cytotoxicity.

Both STAT5a and STAT5b regulate interleukin-7 induced B-cell precursor expansion. STAT5b may also act as a transcriptional inhibitor as demonstrated by inhibition of NF-kB mediated signaling. This STAT5b-mediated inhibitory effect on NF-kB signaling does not depend on STAT5b-DNA interactions but requires the carboxyl terminus of STAT5b as well as STAT5b nuclear translocation and/or accumulation, suggesting that STAT5b is competing for a nuclear factor(s) necessary for NF-kB-mediated activation of target promoters. STAT5 has been theorized to be the physiological substrate of the insulin receptor. In knock-out mice lacking STAT5, no hematopoietic development was impaired; however, STAT5 alpha deficient female mice failed to lactate due to impairment of mammary development. STAT5 has been shown to be the essential mediator of prolactin induced milk protein gene activation.

STAT6 has been shown to be activated by interleukin-4 (IL4), IL13, and IL3. In STAT6 deficient knock-out mice, B lymphocytes fail to proliferate and mature in response to IL4 and T-Lymphocytes differentiation and proliferation is impaired. STAT6 is rapidly tyrosine phosphorylated following stimulation of appropriate cell lines with IL-3, IL-4, epidermal.

Antibody Tools for Detection of STAT Family

Acris Antibodies offers a wide range of antibodies to STAT Transcription Factors. All products provide excellent tools for the detection of STATs by Western blot or other applications like immunoprecipitation or immunohistochemistry.

Fig.1: Induction of phosphorylation of STAT 1 at Ser727 in human malignant melanoma cells (short-term culture derived from a patient) in response to interferons. Subconfluent cells were serum-starved before exposure to activation dosages of IFN-gamma (10 ng/ml) and IFN-alpha (1000 IU/ml and 5000 IU/ml). Western blotting analysis of cell extracts shows detection of phosphorylated STAT1 (Ser727) by the antibody clone PSM1 catno SM3126P (upper panel) and total STAT1 level by the antibody clone SM1 catno SM3125P (lower panel)

Fig. 2-4: Western blotting analysis for STAT2 and STAT5b on Jurkat cells and for STAT6 on K562 cells using polyclonal antibodies cat# SP7181P (STAT2), SP7183P (STAT5b) and SP7184P (STAT6).

Fig. 5: Western blot analysis of phosphorylated Stat6 in NIH 3T3 cells using SM7080P. Lane A: untreated cell lysate. Lane B and C. Anisomycin or EGF treated cell lysates, respectively.

Available Antibody Panel to STAT

Anti- STAT1 (alpha and beta), STAT2, STAT3, STAT4, STAT5 (alpha and beta), STAT6 antibody