BioPAX pathway converted from "Sema3A PAK dependent Axon repulsion" in the Reactome database. Sema3A PAK dependent Axon repulsion Sema3A PAK dependent Axon repulsion This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Activation of PAK by Rac1 Activation of PAK by Rac1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10594171 1 cytosol GO 0005829 PAK1,2,3 dimer [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome http://www.reactome.org Reactome DB_ID: 10594899 1 plasma membrane GO 0005886 Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP [plasma membrane] Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP Reactome DB_ID: 10577354 1 RAC1:GTP [plasma membrane] RAC1:GTP Reactome DB_ID: 29438 1 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI 37565 Reactome DB_ID: 10577352 1 UniProt:Q6LC82 cRac1A Gallus gallus NCBI Taxonomy 9031 UniProt Q6LC82 Chain Coordinates 1 EQUAL 189 EQUAL Reactome Database ID Release 82 10577354 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10577354 Reactome R-GGA-442641 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-442641.1 Reactome DB_ID: 10594897 1 Sema3A:NRP-1:pPlexin-A:Fyn:Fes [plasma membrane] Sema3A:NRP-1:pPlexin-A:Fyn:Fes Reactome DB_ID: 10588531 1 UniProt:A0A1D5PZX7 UniProt A0A1D5PZX7 1 EQUAL 822 EQUAL Reactome DB_ID: 10594895 1 Sema3A:NRP-1:pPlexin-A:fyn [plasma membrane] Sema3A:NRP-1:pPlexin-A:fyn Reactome DB_ID: 10594874 1 extracellular region GO 0005576 Sema3A dimer [extracellular region] Sema3A dimer Reactome DB_ID: 10594872 2 UniProt:R4GJE6 SEMA3A UniProt R4GJE6 21 EQUAL 771 EQUAL Reactome Database ID Release 82 10594874 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594874 Reactome R-GGA-399861 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399861.1 Reactome DB_ID: 10594893 1 NRP1:p-Plexin-A1-4:FYN [plasma membrane] NRP1:p-Plexin-A1-4:FYN Reactome DB_ID: 10588434 1 UniProt:A0A3Q2U639 UniProt A0A3Q2U639 2 EQUAL 537 EQUAL Reactome DB_ID: 10585055 1 UniProt:A0A1L1RW02 UniProt A0A1L1RW02 22 EQUAL 923 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10594891 1 p-Plexin-A1-4 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-PLXNA2 [plasma membrane] phospho-p-Y-PLXNA4 [plasma membrane] phospho-PLXNA1 [plasma membrane] UniProt F1NYZ6 UniProt F1NZB0 UniProt A0A3Q2U4H8 Reactome Database ID Release 82 10594893 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594893 Reactome R-GGA-419625 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419625.1 Reactome Database ID Release 82 10594895 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594895 Reactome R-GGA-419622 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419622.1 Reactome Database ID Release 82 10594897 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594897 Reactome R-GGA-399859 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399859.1 Reactome Database ID Release 82 10594899 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594899 Reactome R-GGA-399872 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399872.1 Reactome DB_ID: 10594901 1 Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAK [plasma membrane] Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAK Converted from EntitySet in Reactome Reactome DB_ID: 10594173 1 PAK1,2,3 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PAK2 [cytosol] PAK3 [cytosol] PAK1 [cytosol] UniProt E1BS97 UniProt F1N8W8 UniProt E1C3P6 Reactome DB_ID: 10594899 1 Reactome Database ID Release 82 10594901 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594901 Reactome R-GGA-399876 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399876.1 Converted from EntitySet in Reactome Reactome DB_ID: 10594173 1 Reactome Database ID Release 82 10594903 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594903 Reactome R-GGA-399930 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399930.1 Plexin-bound Rac1 binds to and stimulates the kinase activity of PAK. PAK dimers are arranged in head-to-tail fashion, in which the catalytic domain binds the kinase inhibitory (KI) domain and is supported by associated PAK-interacting exchange factor (PIX) dimers. Upon Rac1 binding the kinase undergoes conformational change that allows autophosphorylation. Phosphorylation of serine residues disables the KI-domain-kinase interaction and thereby reduces the affinity of PIX. 15548136 Pubmed 2005 PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation Zhao, ZS Manser, E Biochem J 386:201-14 11604131 Pubmed 2001 Plexin signaling via off-track and rho family GTPases Whitford, KL Ghosh, A Neuron 32:1-3 inferred by electronic annotation IEA GO IEA 2.7.11.1 Autophosphorylation of PAK Autophosphorylation of PAK This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 113592 2 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 10594901 1 Reactome DB_ID: 10594953 1 Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAK [plasma membrane] Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAK Converted from EntitySet in Reactome Reactome DB_ID: 10594951 1 p-S,T-PAK1,2,3 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-p-S144,T423-PAK1 [cytosol] phospho-p-S154,T436-PAK3 [cytosol] phospho-p-S141,T402-PAK2 [cytosol] Reactome DB_ID: 10594899 1 Reactome Database ID Release 82 10594953 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594953 Reactome R-GGA-399874 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399874.1 Reactome DB_ID: 29370 2 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10594901 GO 0004674 GO molecular function Reactome Database ID Release 82 10594954 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594954 Reactome Database ID Release 82 10594956 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10594956 Reactome R-GGA-399939 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399939.1 PAK is autophosphorylated at several sites but S-144 flanking the kinase inhibitor region and T-423 (S-141/T-402 in PAK-gamma) within the catalytic domain are the two conserved sites that regulate the catalytic activity. 11278486 Pubmed 2001 The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity Chong, C Tan, L Lim, L Manser, E J Biol Chem 276:17347-53 10075701 Pubmed 1999 Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a function of activation Gatti, A Huang, Z Tuazon, PT Traugh, JA J Biol Chem 274:8022-8 inferred by electronic annotation IEA GO IEA 2.7.11.1 Phosphorylation of LIMK-1 by PAK Phosphorylation of LIMK-1 by PAK This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 113592 1 Reactome DB_ID: 10595082 1 UniProt:Q8QFP8 UniProt Q8QFP8 1 EQUAL 647 EQUAL Reactome DB_ID: 10595085 1 O-phospho-L-threonine at 508 (in Homo sapiens) 508 EQUAL O-phospho-L-threonine [MOD:00047] 1 EQUAL 647 EQUAL Reactome DB_ID: 29370 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10594953 Reactome Database ID Release 82 10595086 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595086 Reactome Database ID Release 82 10595088 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595088 Reactome R-GGA-399952 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399952.1 LIM kinases are serine protein kinases with a unique combination of two N-terminal LIM motifs, a central PDZ domain, and a C-terminal protein kinase domain. LIMK1 is one of the downstream targets of PAK1 and is activated through phosphorylation by PAK1 on T508 within its activation loop (Edwards et al. 1999, Aizawa et al. 2001). LIM-kinase is responsible for the tight regulation of the activity of cofilin (a protein that depolymerizes actin filaments) and thus maintains the balance between actin assembly and disassembly. Phosphorylated cofilin is inactive, resulting in stabilization of the actin cytoskeleton. 11276226 Pubmed 2001 Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse Aizawa, H Wakatsuki, S Ishii, A Moriyama, K Sasaki, Y Ohashi, Ken Sekine-Aizawa, Y Sehara-Fujisawa, A Mizuno, K Goshima, Y Yahara, I Nat Neurosci 4:367-73 10559936 Pubmed 1999 Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics Edwards, DC Sanders, LC Bokoch, GM Gill, GN Nat Cell Biol 1:253-9 inferred by electronic annotation IEA GO IEA Dimerization of LIMK1 by Hsp90 Dimerization of LIMK1 by Hsp90 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10595085 2 O-phospho-L-threonine at 508 (in Homo sapiens) 508 EQUAL 1 EQUAL 647 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10595699 1 HSP90AA1,HSP90AB1 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HSP90AA1 [cytosol] HSP90AB1 [cytosol] UniProt A0A1L1RND0 UniProt F1NC33 Reactome DB_ID: 10595701 1 pLIMK dimer:HSP-90 [cytosol] pLIMK dimer:HSP-90 Reactome DB_ID: 10595085 2 O-phospho-L-threonine at 508 (in Homo sapiens) 508 EQUAL 1 EQUAL 647 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10595699 1 Reactome Database ID Release 82 10595701 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595701 Reactome R-GGA-419632 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419632.1 Reactome Database ID Release 82 10595711 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595711 Reactome R-GGA-419645 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419645.1 After phosphorylation on Thr 508, LIMK undergoes homodimerization. Homodimer formation is promoted by the binding of heat shock protein 90 (Hsp90) to a short sequence in the kinase domain of LIMKs. LIMKs are further phosphorylated after homodimer formation and transphosphorylation of the kinase domain. 16641196 Pubmed 2006 Hsp90 increases LIM kinase activity by promoting its homo-dimerization Li, R Soosairajah, J Harari, D Citri, A Price, J Ng, HL Morton, CJ Parker, MW Yarden, Y Bernard, O FASEB J 20:1218-20 17188549 Pubmed 2007 Lim kinases, regulators of actin dynamics Bernard, O Int J Biochem Cell Biol 39:1071-6 inferred by electronic annotation IEA GO IEA 2.7.11.1 Transphosphorylation of pLIMK1 Transphosphorylation of pLIMK1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 113592 1 Reactome DB_ID: 10595701 1 Reactome DB_ID: 10595706 1 Active LIMK1 [cytosol] Active LIMK1 Reactome DB_ID: 10595704 2 O-phospho-L-threonine at 508 (in Homo sapiens) 508 EQUAL O-phospho-L-serine at unknown position O-phospho-L-serine [MOD:00046] 1 EQUAL 647 EQUAL Reactome Database ID Release 82 10595706 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595706 Reactome R-GGA-419630 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419630.1 Reactome DB_ID: 29370 1 Converted from EntitySet in Reactome Reactome DB_ID: 10595699 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10595701 Reactome Database ID Release 82 10595707 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595707 Reactome Database ID Release 82 10595709 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10595709 Reactome R-GGA-419644 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-419644.1 Binding of Hsp90 to the LIMK proteins protects them from degradation and promotes their dimer formation and transphosphorylation. It is estimated that LIMK1 contains at least 5 phospho-amino acids primarily phospho-serines, in its kinase domain. The positions of these serine residues are not known. Transphosphorylation of these serine residues in LIMK1 increases its stability. 7848918 Pubmed 1994 Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons Bernard, O Ganiatsas, S Kannourakis, G Dringen, R Cell Growth Differ 5:1159-71 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10660706 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10660706 Reactome R-GGA-399954 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-399954.1 Activated Rac1 bound to plexin-A might modulate actin dynamics through the sequential phosphorylation and activation of PAK, LIMK1 and cofilin. 18374575 Pubmed 2008 Semaphorin signaling: progress made and promises ahead Zhou, Y Gunput, RA Pasterkamp, RJ Trends Biochem Sci 33:161-70 12593985 Pubmed 2003 Semaphorin junction: making tracks toward neural connectivity Pasterkamp, RJ Kolodkin, AL Curr Opin Neurobiol 13:79-89 inferred by electronic annotation IEA GO IEA