BRSK2

Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at Thr-529 and Ser-579. Also regulates neuron polarization by mediating phosphorylation of WEE1 at Ser-642 in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress.

Full Name

BR Serine/Threonine Kinase 2

Function

Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (PubMed:22669945).
Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress.

Biological Process

Actin cytoskeleton reorganization Source: UniProtKB
Axonogenesis Source: UniProtKB
Cell division Source: UniProtKB-KW
Cellular response to glucose starvation Source: GO_Central
ERAD pathway Source: ParkinsonsUK-UCL
Establishment of cell polarity Source: UniProtKB
Exocytosis Source: UniProtKB-KW
G2/M transition of mitotic cell cycle Source: UniProtKB
Intracellular signal transduction Source: GO_Central
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
Microtubule cytoskeleton organization involved in establishment of planar polarity Source: ARUK-UCL
Neuron differentiation Source: UniProtKB
Peptidyl-serine phosphorylation Source: Ensembl
Protein phosphorylation Source: UniProtKB
Regulation of ATPase activity Source: ParkinsonsUK-UCL
Regulation of axonogenesis Source: ARUK-UCL
Regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
Regulation of neuron projection development Source: ARUK-UCL
Regulation of retrograde protein transport, ER to cytosol Source: ParkinsonsUK-UCL
Regulation of synaptic vesicle clustering Source: ARUK-UCL

Cellular Location

Endoplasmic reticulum; Centrosome; Perinuclear region. Detected at centrosomes during mitosis. Localizes to the endoplasmic reticulum in response to stress caused by tunicamycin.

PTM

Phosphorylated at Thr-174 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-174 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-174 by PP2C. Phosphorylated at Thr-260 by PKA. Phosphorylation at Thr-260 by PKA was not observed in another study (PubMed:18339622), but this may reflect differences in the experimental approach. Phosphorylation at Thr-260 seems to play a role in the regulation of insulin secretion (PubMed:22669945).
Polyubiquitinated by the APC complex in conjunction with FZR1, leading to its proteasomal degradation. Targeted for proteasomal degradation by interaction with COPS5. BRSK2 levels change during the cell cycle. BRSK2 levels are low at the G1/S boundary and gradually increase as cells progress into G2 phase. BRSK2 levels decrease rapidly at the end of mitosis.