What is the function of LKB1?

What is the function of LKB1?

Liver kinase B1 (LKB1, also known as STK11 or Par-4) is a ubiquitously expressed master serine/threonine kinase that plays crucial roles in numerous cellular events, such as polarity control, proliferation, differentiation and energy homeostasis, in many types of cells by activating downstream kinases of the AMP- …

What activates LKB1?

LKB1 activation is governed by a phosphorylation-independent allosteric mechanism in which it forms a heterotrimeric complex with 2 accessory proteins, STE20-related kinase adaptor (STRAD) and mouse protein 25 (MO25, also known as calcium binding protein 39, CAB39).

Is LKB1 a tumor suppressor?

The LKB1 tumour suppressor is a serine/threonine kinase that functions as master regulator of cell growth, metabolism, survival and polarity. LKB1 is frequently mutated in human cancers and research spanning the last two decades have begun decoding the cellular pathways deregulated following LKB1 inactivation.

What is the role of LKB1 AMPK in metabolic regulation?

LKB1/AMPK maintains cell polarity and inhibits cell proliferation and energy metabolism. Moreover, recent studies demonstrated that the LKB1/AMPK pathway plays an important role in the invasion and migration of tumor cells by regulating gene expression and activation of multiple signaling pathways.

What is LKB1 gene?

The STK11 gene (also called LKB1) provides instructions for making an enzyme called serine/threonine kinase 11. This enzyme is a tumor suppressor, which means that it helps keep cells from growing and dividing too fast or in an uncontrolled way.

What does LKB1 stand for?

The Liver Kinase B1 (LKB1) is a central regulator of T cell development, activation, and metabolism.

What is upstream of LKB1?

The kinases AKT and LKB1 display antagonistic functions to control cell proliferation: AKT activates mTOR signaling, whereas LKB1 inhibits it via AMPK activation [83, 84]. However, AKT act as an upstream regulator of LKB1, as it directly phosphorylates S334 of LKB1.

What is pjs medical?

Peutz-Jeghers syndrome (PJS) is an inherited condition that puts people at an increased risk for developing hamartomatous polyps in the digestive tract, as well as cancers of the breast, colon and rectum, pancreas, stomach, testicles, ovaries, lung, cervix, and other types listed below.

What phosphorylates AMPK?

AMPK activity is stimulated more than 100-fold by phosphorylation of threonine 172 (Thr172). Binding of AMP to the γ subunit allosterically activates the kinase. However, in a cellular context, phosphorylation of Thr172 is critical for significant activation of AMPK.

Is LKB1 the same as STK11?

Is STK11 an oncogene?

STK11 is a tumor suppressor gene, and loss‐of‐function mutations are oncogenic, due at least in part to loss of AMPK regulation of mTOR and HIF‐1‐α. Clinical trials are under way, offering hope to patients whose STK11‐mutated tumors are refractory and/or have progressed on chemotherapeutic regimens.

Are hamartomatous polyp cancerous?

Though most of the gastric hamartomatous polyps are benign, certain types are associated with increased malignant potential. These include certain polyps associated with specific genetic familial polyposis syndromes and gastric inverted hamartomatous polyps.

How does LKB1 activate AMPK?

In the past decade, studies of the human tumour suppressor LKB1 have uncovered a novel signalling pathway that links cell metabolism to growth control and cell polarity. LKB1 encodes a serine–threonine kinase that directly phosphorylates and activates AMPK, a central metabolic sensor.

Is LKB1 a tumor suppressor or carcinogen?

This carcinogenic effect contradicts the previous conclusion that LKB1 is a tumor suppressor gene. Here we try to explain the contradictory effect of LKB1 on cancer from a metabolic perspective. Upon deletion of LKB1, cancer cells experience increased energy as well as oxidative stress, thereby causing genomic instability.

Liver kinase B1 (LKB1; UniProt：Q15831) is an essential serine/threonine kinase that regulates various cellular processes, including cell metabolism, cell polarity, and apoptosis. Comprehensive functional information on LKB1 is accessible through UniProt Knowledgebase (UniProtKB: https://www.uniprot.org ).

Is AMPK a tumor suppressor?

AMPK is an essential mediator of the tumor suppressor LKB1 and could be suppressed in cancer cells containing loss-of-function mutations of LKB1or containing active mutations of B-Raf, or in cancers associated with metabolic syndrome.