LATS2
LATS2 (large tumour suppressor kinase 2) is a serine/threonine protein kinase and a core component of the Hippo signalling pathway, where it negatively regulates YAP1. It acts as a tumour suppressor that restricts proliferation, promotes apoptosis and helps maintain mitotic fidelity. Browse Assay Genie's current range of LATS2 research reagents below, or read on for the biology behind the target.
LATS2 is a negative regulator of YAP1 in the Hippo signalling pathway, which plays a pivotal role in organ size control and tumour suppression by restricting proliferation and promoting apoptosis. The core of the pathway is a kinase cascade in which STK3/MST2 and STK4/MST1, in complex with SAV1, phosphorylate and activate LATS1/2 in complex with MOB1. LATS kinases then phosphorylate and inactivate the YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus, where it would regulate genes important for cell proliferation, cell death and cell migration. LATS2 also phosphorylates YAP1 following WWP1 ubiquitination of AMOTL2 during cell contact inhibition.
Beyond Hippo signalling, LATS2 has a role in centrosome duplication, mitotic fidelity and genomic stability. It negatively regulates the G1/S transition by down-regulating cyclin E/CDK2 kinase activity. The protein localises to centrosomes during interphase and early and late metaphase, interacts with aurora-A and ajuba, and is required for gamma-tubulin accumulation and spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may act in a positive feedback loop with p53 in response to cytoskeleton damage. LATS2 negatively regulates the androgen receptor and can act as a co-repressor of androgen-responsive gene expression.
LATS2 also has context-dependent activities. It phosphorylates SNAI1 in the nucleus, leading to nuclear retention and stabilisation, which enhances epithelial-mesenchymal transition and tumour cell invasion and migration, independently of YAP1 or WWTR1/TAZ. It activates the NLRP3 inflammasome by phosphorylating Ser-265 of NLRP3 after palmitoylation, promoting NLRP3 activation by NEK7. The LATS2 gene belongs to the large tumour suppressor kinase family, and the protein is a member of the AGC Ser/Thr protein kinase family within the protein kinase superfamily. The mouse ortholog is Lats2.
LATS2 phosphorylates and inactivates YAP1 and WWTR1/TAZ downstream of STK3/MST2, STK4/MST1, SAV1 and MOB1, making it central to studies of organ size control.
LATS2 restricts proliferation, promotes apoptosis and supports genomic stability, while also phosphorylating SNAI1 to enhance invasion and migration.
LATS2 localises to centrosomes and spindle poles, interacts with aurora-A and ajuba, and is needed for gamma-tubulin accumulation and spindle formation.
LATS2 phosphorylates NLRP3 to promote activation by NEK7, and acts as a negative regulator and co-repressor of androgen receptor signalling.
LATS2 is a Hippo pathway kinase that phosphorylates YAP1 and WWTR1/TAZ, preventing YAP1 from entering the nucleus to drive proliferation and migration genes. It also supports centrosome duplication and mitotic fidelity, and down-regulates cyclin E/CDK2 activity to restrain the G1/S transition.
The HGNC name is large tumour suppressor kinase 2. Previous names are LATS (large tumour suppressor, Drosophila) homolog 2, and UniProt lists it as serine/threonine-protein kinase LATS2. It belongs to the large tumour suppressor kinase family and the AGC Ser/Thr protein kinase family.
Mostly, but not exclusively. LATS2 acts as a tumour suppressor through YAP1 inhibition and mitotic control. However, it phosphorylates SNAI1 in the nucleus, stabilising it and enhancing invasion, independently of YAP1 or TAZ. Check the datasheet of any product for its validated reactivity, including mouse Lats2.
LATS1, Hippo pathway kinases and effectors, and partners in mitosis and inflammasome signalling with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NRM7; product specifications from Assay Genie datasheets.