Signaling by PTK6 (Homo sapiens)

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1, 6, 9, 12, 15...69563, 145, 15622, 10114054, 122, 1319582952340, 117105, 164823527, 10033231141142210027, 10010210512282825451, 67, 11418, 70, 92, 9984, 103, 121709546, 776346, 1451176383, 10411484, 1213561011019510254104114cytosolnucleoplasmHBEGF:EGFR:p-Y525-GPNMBp-Y342-PTK6 UBC(381-456) ADPADPp-Y31,Y118-PXNHRAS Signaling by EGFRPTPN1 ADPRegulation ofHypoxia-inducibleFactor (HIF) byoxygenp-Y342-PTK6:ARHGAP35DOCK1 CDK4 ADPCDKN1B:(CDK4:CCND1,(CDK2:CCNE1))p-Y525-GPNMB ATPATPCCNE1 p-Y435,Y440,Y443-KHDRBS1p-Y342-PTK6:AKT1PTK6 GeneARAP1 p-Y342-PTK6RHOA UBB(1-76) p-Y165,Y664-BCAR1p-Y342-PTK6 p-Y705-STAT3 ARHGAP35 p-Y231-ARAP1HIF1A,EPAS1:PTK6Genep-Y342-PTK6 ADPLRRK2p-Y342-PTK6 KRAS HBEGF(63-148) p-Y342-PTK6 GTP KRAS SOCS3 GeneHBEGF:EGFR:p-Y525-GPNMB:LINC01139:PTK6:LRRK2RHO GTPases activateCITp-Y342-PTK6 Phosphorylated p-Y877-ERBB2 heterodimers PTK6 Gene EPAS1 KHDRBS2p-Y342-PTK6:CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ELMO2 CBLp-Y1105-ARHGAP35RPS27A(1-76) BCAR1NRAS p-Y525-GPNMB SOCS3LINC01139GDPp-Y362-DOK1RASA1 ATPRHO GTPases activateIQGAPsPTK6 Gene p-Y342-PTK6 H2Op-Y342-PTK6:p-Y250-STAP2p-Y342-PTK6 STAP2p-Y1105-ARHGAP35:RHOA:GTPp-Y1105-ARHGAP35:RASA1BCAR1 p-Y342-PTK6:BCAR1PELP1RHO GTPases ActivateWASPs and WAVEsp-Y88-CDKN1B DOK1UBC(1-76) SemaphorininteractionsADPCCND1 HBEGF(63-148) GPNMBGDP UBA52(1-76) p-Y342-PTK6 HBEGF(63-148) RHOA LRRK2 p-Y342-PTK6DOK1 RHO GTPases activateKTN1UBB(153-228) AKT1EGFR p-Y705-STAT3ADPGDP NRAS HBEGF:EGFR:GPNMBHBEGF:EGFR:p-Y525-GPNMB:LINC01139:p-Y351-PTK6:LRRK2p-Y351-PTK6 NR3C1:DexamethasonePXNPTK6Gene:EPAS1:NR3C1:Dexamethasone:PELP1p-Y705-STAT3dimer:SOCS3 GeneATPSOCS3 GTP KHDRSB3p-Y705-STAT3 CCND1 p-Y88-CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))PIP3 activates AKTsignalingKRAS Phosphorylated p-Y877-ERBB2 heterodimers p-Y342-PTK6:PTPN1PiATPADPDEXA UBB(77-152) PolyUb,p-Y700,Y731,Y774-CBLELMO1 PELP1 p-Y565,S797-HIF1ADEXA NR3C1 ADPCDK2 p-Y31,Y118-PXN:CRK:DOCK180:ELMO1,ELMO2RAF/MAP kinasecascadep-Y435,Y440,Y443-KHDRBS1CDK2 CRK LRRK2 ATPCRK EPAS1 PTK6p-Y342-PTK6 RAC1:GTPp-Y342-PTK6:SOCS3ADPp-Y342-PTK6:PXNPhosphorylated p-6Y-ERBB2 heterodimers UBC(609-684) RHOA:GTPHBEGF:EGFRNR3C1 p-Y250-STAP2 ATPPTK6 NRAS EGFR ATPHIF1A,EPAS1p-Y342,Y447-PTK6p-Y342-PTK6:KHDRBS1PiRHO GTPases activatePKNsADPATPLINC01139 p-Y-KHDRBS2p21 RAS:GTPATPHBEGF(63-148) GTP LINC01139 ATPUbUBC(229-304) KHDRBS1 HRAS p-Y342-PTK6 UBC(533-608) RHO GTPases activatePAKsCCNE1 p-Y250-STAP2 RASA1UBC(153-228) p-Y-SFPQp-Y700,Y731,Y774-CBLEGFR SFPQCDKN1B p-Y-KHDRSB3CDKN1B Signaling by ERBB2EPAS1 ADPp-Y342-PTK6:p-Y250-STAP2:STAT3GTP CDK4 RAC1 ADPGTP p-Y342-PTK6 EGFR RAC1 p21 RAS:GTP:RASA1CDK4 p-Y1105-ARHGAP35 EGFR p21 RAS:GDPKHDRBS1S Phasep-Y1105-ARHGAP35 p-ERBB2heterodimers:PTK6p-Y525-GPNMB PTK6 CRK:DOCK180:ELMO1,ELMO2HIF1AAKT1 RHOA p-Y31,Y118-PXN Phosphorylated p-6Y-ERBB2 heterodimers p-Y315,Y326-AKT1 DOCK1 EPAS1ATPELMO1 CCNE1 CDK2 ATPUBC(457-532) CCND1 PTPN1HRAS ARAP1RHO GTPases ActivateForminsATPp-Y705-STAT3 dimerUBC(77-152) p-ERBB2 heterodimersADPUBC(305-380) RASA1 p-Y342-PTK6 p-Y705-STAT3 dimerSTAT3 SRMSADPSOCS3 Gene p-Y342-PTK6:p-Y315,Y326-AKT1STAT3ELMO2 STAP2 p-Y342-PTK6 GDP RHOA:GDPp-Y342-PTK6:ARAP1GPNMB ATPp-Y705-STAT3 Mitotic G1-G1/SphasesHBEGF(63-148) GTPp-Y342-PTK6:STAP2HIF1A p-Y342-PTK6:DOK1HIF1A RAC1:GDPARHGAP35PXN 17, 52, 69, 94, 108...3, 7, 20, 30, 38...821145, 10, 16, 26, 42...667, 114952, 37, 57, 62, 68...951006363, 15613, 24, 32, 55, 59...95105, 16461, 88, 119, 15111, 34, 91, 96, 107...1022228, 4910154278210514, 25, 39, 44, 113...4, 8, 19, 29, 41...351142231, 43, 79, 143, 15384869511777


Description

PTK6 (BRK) is an oncogenic non-receptor tyrosine kinase that functions downstream of ERBB2 (HER2) (Xiang et al. 2008, Peng et al. 2015) and other receptor tyrosine kinases, such as EGFR (Kamalati et al. 1996) and MET (Castro and Lange 2010). Since ERBB2 forms heterodimers with EGFR and since MET can heterodimerize with both ERBB2 and EGFR (Tanizaki et al. 2011), it is not clear if MET and EGFR activate PTK6 directly or act through ERBB2. Levels of PTK6 increase under hypoxic conditions (Regan Anderson et al. 2013, Pires et al. 2014). The kinase activity of PTK6 is negatively regulated by PTPN1 phosphatase (Fan et al. 2013) and SRMS kinase (Fan et al. 2015), as well as the STAT3 target SOCS3 (Gao et al. 2012).

PTK6 activates STAT3-mediated transcription (Ikeda et al. 2009, Ikeda et al. 2010) and may also activate STAT5-mediated transcription (Ikeda et al. 2011). PTK6 promotes cell motility and migration by regulating the activity of RHO GTPases RAC1 (Chen et al. 2004) and RHOA (Shen et al. 2008), and possibly by affecting motility-related kinesins (Lukong and Richard 2008). PTK6 crosstalks with AKT1 (Zhang et al. 2005, Zheng et al. 2010) and RAS signaling cascades (Shen et al. 2008, Ono et al. 2014) and may be involved in MAPK7 (ERK5) activation (Ostrander et al. 2007, Zheng et al. 2012). PTK6 enhances EGFR signaling by inhibiting EGFR down-regulation (Kang et al. 2010, Li et al. 2012, Kang and Lee 2013). PTK6 may also enhance signaling by IGF1R (Fan et al. 2013) and ERBB3 (Kamalati et al. 2000).<p>PTK6 promotes cell cycle progression by phosphorylating and inactivating CDK inhibitor CDKN1B (p27) (Patel et al. 2015).<p>PTK6 activity is upregulated in osteopontin (OPN or SPP1)-mediated signaling, leading to increased VEGF expression via PTK6/NF-kappaB/ATF4 signaling path. PTK6 may therefore play a role in VEGF-dependent tumor angiogenesis (Chakraborty et al. 2008).<p>PTK6 binds and phosphorylates several nuclear RNA-binding proteins, including SAM68 family members (KHDRSB1, KHDRSB2 and KHDRSB3) (Derry et al. 2000, Haegebarth et al. 2004, Lukong et al. 2005) and SFPQ (PSF) (Lukong et al. 2009). The biological role of PTK6 in RNA processing is not known.<p>For a review of PTK6 function, please refer to Goel and Lukong 2015. View original pathway at:Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8848021
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

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History

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CompareRevisionActionTimeUserComment
102035view16:22, 26 November 2018Marvin M2Ontology Term : 'PW:0000003' removed !
102034view16:21, 26 November 2018Marvin M2Ontology Term : 'kinase mediated signaling pathway' added !
101698view14:35, 1 November 2018DeSlOntology Term : 'signaling pathway' added !
101490view11:35, 1 November 2018ReactomeTeamreactome version 66
101027view21:15, 31 October 2018ReactomeTeamreactome version 65
100725view20:11, 31 October 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AKT1 ProteinP31749 (Uniprot-TrEMBL)
AKT1ProteinP31749 (Uniprot-TrEMBL)
ARAP1 ProteinQ96P48 (Uniprot-TrEMBL)
ARAP1ProteinQ96P48 (Uniprot-TrEMBL)
ARHGAP35 ProteinQ9NRY4 (Uniprot-TrEMBL)
ARHGAP35ProteinQ9NRY4 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
BCAR1 ProteinP56945 (Uniprot-TrEMBL)
BCAR1ProteinP56945 (Uniprot-TrEMBL)
CBLProteinP22681 (Uniprot-TrEMBL)
CCND1 ProteinP24385 (Uniprot-TrEMBL)
CCNE1 ProteinP24864 (Uniprot-TrEMBL)
CDK2 ProteinP24941 (Uniprot-TrEMBL)
CDK4 ProteinP11802 (Uniprot-TrEMBL)
CDKN1B ProteinP46527 (Uniprot-TrEMBL)
CDKN1B:(CDK4:CCND1,(CDK2:CCNE1))ComplexR-HSA-8848419 (Reactome)
CRK ProteinP46108 (Uniprot-TrEMBL)
CRK:DOCK180:ELMO1,ELMO2ComplexR-HSA-2029141 (Reactome)
DEXA MetaboliteCHEBI:41879 (ChEBI)
DOCK1 ProteinQ14185 (Uniprot-TrEMBL)
DOK1 ProteinQ99704 (Uniprot-TrEMBL)
DOK1ProteinQ99704 (Uniprot-TrEMBL)
EGFR ProteinP00533 (Uniprot-TrEMBL)
ELMO1 ProteinQ92556 (Uniprot-TrEMBL)
ELMO2 ProteinQ96JJ3 (Uniprot-TrEMBL)
EPAS1 ProteinQ99814 (Uniprot-TrEMBL)
EPAS1ProteinQ99814 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GPNMB ProteinQ14956 (Uniprot-TrEMBL)
GPNMBProteinQ14956 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HBEGF(63-148) ProteinQ99075 (Uniprot-TrEMBL)
HBEGF:EGFR:GPNMBComplexR-HSA-8857546 (Reactome)
HBEGF:EGFR:p-Y525-GPNMB:LINC01139:PTK6:LRRK2ComplexR-HSA-8857567 (Reactome)
HBEGF:EGFR:p-Y525-GPNMB:LINC01139:p-Y351-PTK6:LRRK2ComplexR-HSA-8857574 (Reactome)
HBEGF:EGFR:p-Y525-GPNMBComplexR-HSA-8857556 (Reactome)
HBEGF:EGFRComplexR-HSA-8857547 (Reactome)
HIF1A ProteinQ16665 (Uniprot-TrEMBL)
HIF1A,EPAS1:PTK6 GeneComplexR-HSA-8848808 (Reactome)
HIF1A,EPAS1ComplexR-HSA-8848802 (Reactome)
HIF1AProteinQ16665 (Uniprot-TrEMBL)
HRAS ProteinP01112 (Uniprot-TrEMBL)
KHDRBS1 ProteinQ07666 (Uniprot-TrEMBL)
KHDRBS1ProteinQ07666 (Uniprot-TrEMBL)
KHDRBS2Prot