PTK6 - Protein-tyrosine kinase 6 - human protein (Function)
 
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads
Back to ...  
Publication View
Protein
Gene
References

 
PTK6 »  Protein-tyrosine kinase 6   [ EC 2.7.10.2 ]
 
Protein also known as:  Tyrosine-protein kinase BRK.
Gene name:  PTK6
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 80 2
GENE REF ISO

Function

 show evidences
Overview 
Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.  
9
  • CuratedUniProtKB
Isoform  Iso 2   Inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.  
9
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
2
  • IPIIntAct
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
5
  • IPIIntAct
  • IPIUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674] silver  
  • IEAOrtholog Compara
GO biological process 
Cell migrationdefinition[GO:0016477]  
1
  • IDAUniProtKB
Cellular response to retinoic aciddefinition[GO:0071300]  
1
  • IMPBHF-UCL
Intestinal epithelial cell differentiationdefinition[GO:0060575] silver  
  • IEAOrtholog Compara
Negative regulation of growthdefinition[GO:0045926] silver  
  • IEAOrtholog Compara
Negative regulation of protein tyrosine kinase activitydefinition[GO:0061099]  
1
  • IDAUniProtKB
Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • IMPBHF-UCL
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IMPUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Tyrosine phosphorylation of Stat3 proteindefinition[GO:0042503]  
1
  • IDAUniProtKB
Tyrosine phosphorylation of Stat5 proteindefinition[GO:0042506]  
1
  • IDAUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by EGF, NRG1 and IGF1. Inhibited by SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region. Interaction between Trp-184 within SH2-TK linker region and the catalytic domain appears essential for positive regulation of kinase activity.  
5
  • CuratedUniProtKB
 
More information is available from:
 

Biophysicochemical properties

Kinetic parameters
KM 83 uM for ATP
Vmax 37 nmol/min/mg enzyme

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PTK6
GenomeRNAi: 5753
PRO: PR:Q13882
Chemistry
GuidetoPHARMACOLOGY: 2182