bioax途径由Reactome数据库中的“PAK1的自磷酸化”转化而来。

2.7.11

PAK1的自身磷酸化

PAK1需要自磷酸化才能完全激活。PAK1在几个位点上发生了自磷酸化，但激酶抑制剂区域两侧的S144和催化域内的T423是调节催化活性的两个保守位点(Chong et al. 2001, Parrini et al. 2001)。

作者:Garapati, P V, 2012-01-04 Rosales, C, 2012-05-14 评论:Rivero Crespo, Francisco, 2014-12-26 编辑:Garapati, P V, 2012-01-04 编辑：Orlic-Milacic，Marija，2017-03-15

Reactome DB_ID: 2029159

等离子体膜去 0005886 RAC1：GTP，CDC42：GTP：PAK1 [血浆膜]

RAC1:三磷酸鸟苷,CDC42:三磷酸鸟苷:PAK1

从Reactome中的EntitySet转换而来

Reactome DB_ID: 389778

CDC42:GTP, RAC1:GTP[质膜] 从Reactome中的EntitySet转换而来。每个同义词是一个PhysicalEntity的名称，每个XREF指向一个PhysicalEntity Reactome //www.joaskin.com

Reactome DB_ID: 162629

胞质去 0005829

UniProt: Q13153 PAK1

PAK1

PAK1 功能蛋白激酶参与整合素和受体激酶下游的细胞内信号通路，在细胞骨架动力学、细胞粘附、迁移、增殖、凋亡、有丝分裂和囊泡介导的运输过程中发挥重要作用(PubMed:30290153)。可直接使BAD磷酸化，保护细胞不凋亡。由CDC42和RAC1相互作用激活。作为GTPase效应器，将rho相关的GTPases CDC42和RAC1连接到JNK MAP激酶通路。磷酸化并激活MAP2K1，从而介导下游MAP激酶的激活。参与肌动蛋白细胞骨架、肌动蛋白应力纤维和局部黏附复合体的重组。磷酸化微管蛋白伴侣TBCB，从而在微管生物发生和微管蛋白细胞骨架组织中发挥调节作用。在调节胰岛素分泌以应对葡萄糖水平升高方面发挥作用。包含PAK1, DVL1和麝香的三元复合物的一部分，在神经肌肉连接(NMJ)形成过程中，对麝香依赖的AChR聚集调控非常重要。CDC2L1和CDC2L2的结合可能会抑制细胞凋亡的活性。 Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667).ACTIVITY REGULATION Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423.SUBUNIT Homodimer; homodimerization results in autoinhibition (PubMed:30290153). Active as monomer. Component of cytoplasmic complexes, which also contains PXN, ARHGEF6 and GIT1. Interacts with NISCH (By similarity). Interacts with DVL1; mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By similarity). Binds to the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not the full-length proteins (PubMed:12624090). Interacts with ARHGEF7 (PubMed:16101281). Interacts tightly with GTP-bound but not GDP-bound CDC42/P21 and RAC1 (By similarity). Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM (via cytoplasmic domain); the interaction is direct and enhanced in presence of RAC1 (PubMed:15169762). Interacts with SCRIB (PubMed:18716323). Interacts with PDPK1 (PubMed:10995762). Interacts (via kinase domain) with RAF1 (PubMed:11733498). Interacts with NCK1 and NCK2 (PubMed:10026169). Interacts with TBCB (PubMed:15831477). Interacts with CRIPAK (PubMed:16278681). Interacts with BRSK2 (By similarity). Interacts with SNAI1 (PubMed:15833848). Interacts with CIB1 isoform 2 (PubMed:23503467). Interacts with CIB1 (via N-terminal region); the interaction is direct, promotes PAK1 activity and occurs in a calcium-dependent manner. Interacts with INPP5K (PubMed:26940976).TISSUE SPECIFICITY Overexpressed in gastric cancer cells and tissues (at protein level) (PubMed:25766321).PTM Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one. Activated by autophosphorylation at Thr-423 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation at Thr-423 by BRSK2 and by PDPK1. Phosphorylated by JAK2 in response to PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT; this reduces interaction with NCK1 and association with focal adhesion sites. Upon DNA damage, phosphorylated at Thr-212 and translocates to the nucleoplasm (PubMed:23260667). Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (By similarity).SIMILARITY Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. 智人

NCBI分类法 9606 UniProt Q13153

链坐标

平等的

545

平等的

Reactome数据库ID Release 77 2029159 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=2029159 Reactome r - hsa - 2029159

Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2029159.3

Reactome DB_ID: 113592

ATP (4 -) (ChEBI: 30616)

ATP (4)

腺苷5 '三磷酸三磷酸腺苷 atp. ChEBI 30616

Reactome DB_ID: 29370

ADP (3 -) (ChEBI: 456216)

ADP (3 -)

ADP trianion 事情就让它5,- o - [(phosphonatooxy) phosphinato]腺苷 ADP ChEBI 456216 从Reactome中的EntitySet转换而来

Reactome DB_ID: 389778

Reactome DB_ID: 399819

O-phospho-L-serine在144

144

平等的

O-phospho-L-serine (MOD: 00046)

O-phospho-L-threonine在423

423

平等的

O-phospho-L-threonine (MOD: 00047)

平等的

545

平等的

PHYSIOL-LEFT-TO-RIGHT

激活

Reactome DB_ID: 162629

平等的

545

平等的

去 0004674

去分子功能

Reactome数据库ID Release 77 445074 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=445074 Reactome数据库ID Release 77 2029454 数据库标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=2029454 Reactome r - hsa - 2029454

Reactome稳定的标识符。使用此URL连接到Reactome中的此实例的网页://www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2029454.4 11804587 Pubmed 2002 Pak1激酶同源二聚体在反式中被自动抑制，并在Cdc42和Rac1激活时解离 Parrini, MC Lei, M 哈里森,SC Mayer, BJ 摩尔细胞9:73 - 83 11278486 Pubmed 2001 PAK活化机制。自磷酸化事件在调节和激酶域控制活性庄,C 谭,我老林,我 Manser，E. J Biol Chem 276:17347-53