Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:26246606, PubMed:12390251, PubMed:18615013, PubMed:11039908, PubMed:17125279, PubMed:17360485). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:26246606, PubMed:14523000). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:18056443, PubMed:15128871, PubMed:14702041, PubMed:11551964, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18615013). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Necessary for proper cilia disassembly prior to mitosis (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735). {ECO:0000269|PubMed:11039908, ECO:0000269|PubMed:11551964, ECO:0000269|PubMed:12390251, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:14523000, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15128871, ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:15987997, ECO:0000269|PubMed:17125279, ECO:0000269|PubMed:17360485, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19668197, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:27335426, ECO:0000269|PubMed:28218735}.

Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}.

Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution. {ECO:0000269|PubMed:12393264, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15992363, ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17121855, ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17611284, ECO:0000269|PubMed:17671990, ECO:0000269|PubMed:18042622, ECO:0000269|PubMed:19081376, ECO:0000269|PubMed:19693690, ECO:0000269|PubMed:20061803, ECO:0000269|PubMed:20213743, ECO:0000269|PubMed:20826806, ECO:0000269|PubMed:21209322, ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:21442427, ECO:0000269|PubMed:21465480, ECO:0000269|PubMed:21499257, ECO:0000269|PubMed:24235147, ECO:0000269|PubMed:9822744}.

Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (By similarity). {ECO:0000250|UniProtKB:P39688, ECO:0000269|PubMed:11005864, ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11536198, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:14707117, ECO:0000269|PubMed:14761972, ECO:0000269|PubMed:15536091, ECO:0000269|PubMed:15557120, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:16841086, ECO:0000269|PubMed:17194753, ECO:0000269|PubMed:18056706, ECO:0000269|PubMed:18258597, ECO:0000269|PubMed:19179337, ECO:0000269|PubMed:19652227, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:7568038, ECO:0000269|PubMed:7822789}.

Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:7687428}.

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}.

PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.

Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984}.; [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}.

Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10579722, ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}.