Product Name:

LATS1-pS909


Product Number:

ab-pk678

Price:

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$98.00
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Target Full Name: Large tumour suppressor 1 protein-serine kinase (WARTS)

Target Alias: Large tumour suppressor 1; LATS, large tumour suppressor, 1; WARTS; wts; ENSG00000131023

Product Type Specific: LATS1 protein kinase phosphosite-specific antibody

Antibody Code: PK678

Antibody Target Type: Phosphosite-specific

Antibody Phosphosite: S909

Protein UniProt: O95835

Protein SigNET: LATS1

Antibody Type: Polyclonal

Antibody Host Species: Rabbit

Antibody Immunogen Source: Human LATS1 sequence peptide Cat. No.: PE-04ANH99

Antibody Immunogen Sequence: LAH(pS)LVG(bA)C

Antibody Immunogen Description: Corresponds to amino acid residues L906 to G912. S909 phosphorylation stimulates phosphotransferase activity. This phosphosite is located in the kinase activation loop between catalytic subdomains VII and VIII. This is one of the major in vivo phosphorylation sites in LATS1 (≥13 reports from high throughput mass spectrometry studies recorded in PhosphoSitePlus). LATS1 is known to be phosphorylated at this site in vitro by LATS1, and MST2 (CLIK1, STK3).

Production Method: The immunizing peptide was produced by solid phase synthesis on a multipep peptide synthesizer and purified by reverse-phase hplc chromatography. Purity was assessed by analytical hplc and the amino acid sequence confirmed by mass spectrometry analysis. This peptide was coupled to KLH prior to immunization into rabbits. New Zealand White rabbits were subcutaneously injected with KLH-coupled immunizing peptide every 4 weeks for 4 months. The sera from these animals was applied onto an agarose column to which the immunogen peptide was thio-linked. Antibody was eluted from the column with 0.1 M glycine, pH 2.5. Subsequently, the antibody solution was neutralized to pH 7.0 with saturated Tris.This antibody was also subject to negative purification over phosphotyrosine-agarose.

Antibody Modification: Unconjugated. Contact KInexus if you are interest in having the antibody biotinylated or coupled with fluorescent dyes.

Antibody Concentration: 1 mg/ml

Storage Buffer: Phosphate buffered saline pH 7.4, 0.05% Thimerasol

Storage Conditions: For long term storage, keep frozen at -40°C or lower. Stock solution can be kept at +4°C for more than 3 months. Avoid repeated freeze-thaw cycles.

Product Use: Western blotting | Antibody microarray

Antibody Dilution Recommended: 2 µg/ml for immunoblotting

Antibody Potency: Very weak immunoreactivity of a target-sized protein by Western blotting in MCF7 cells. Very strong immunoreactivity with immunogen peptide on dot blots.

Antibody Species Reactivity: This antibody detects the target phosphoprotein in the following species due to conservation of amino acid sequence: Human | Chimpanzee | Dog | Mouse | Platypus | Chicken | Frog | Zebra fish | Sea urchin.

Antibody Positive Control: The observed molecular mass of the processed target protein on SDS-PAGE gels is reported to be around 140-170 kDa.

Antibody Specificity: Very high

Antibody Cross Reactivity: No significant cross-reactivities in HeLa and MCF7 cells or in sea star oocytes.

Scientific Background: LATS1 (WARTS) is a protein-serine/threonine kinase of the AGC group and NDR family, and its features a C-terminal kinase domain and an N-terminal region with two PPxY motifs that bind to WW-domain proteins like YAP1/TAZ. It also binds to actin. LATS1 appears to be a tumour suppressor protein (TSP) in the Hippo signalling pathway, although it undergoes a typical rate of bystander mutations in human cancers. The active form of the protein kinase normally inhibits tumour cell proliferation. As a core component of the Hippo pathway, LATS1 is phosphorylated and activated by MST1/2 kinases (or MAP4Ks) at Ser-909 and Thr-1079. This subsequently enables LATS1 to phosphorylate and inhibit the transcriptional co-activators TAZ and YAP1, inhibiting the oncogene actions of YAP1. The phosphorylated and inactivated YAP1 is blocked in its translocation to the nucleus for transcription of genes important for proliferation and migration. It also promotes apoptosis by activating the transcription of BAX, caspase 3 and p53. NUAK1 and NUAK2 mediated Ser-464 phosphorylation and induced degradation of LATS1 can be inhibited with a LATS1 mutation of S464A. Inhibition of LATS1-YAP1 interaction can occur with a Y559F mutation. The K734A mutation can abrogate kinase phosphotransferase activity, reduce 53 translation, increase time for mitosis, autophosphorylation, and increase ploidy. LATS1 localizes to the mitotic apparatus (centrosomes and spindle poles) during mitosis and regulates the G1/S and G2/M transitions. It negatively regulates the G2/M transition by downregulating CDK1 phosphotransferase activity. M669I and R806P mutations have been associated with lung adenocarcinoma and lung large cell carcinoma, respectively. Decreased LATS1 expression due to hypermethylation of the promoter have been associated with breast cancer, acute lymphoblastic leukemia, ovarian cancer, and astrocytoma. However, the very low frequency of reported somatic mutations in this protein indicates that it may function as a tumour requiring protein (TRP) in many human tumours. This description may include information annotated by UniProt and/or Google AI.