InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PTK6

Summary

InnateDB Protein

IDBP-86383.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PTK6

Protein Name

PTK6 protein tyrosine kinase 6

Synonyms

BRK;

Species

Homo sapiens

Ensembl Protein

ENSP00000217185

InnateDB Gene

IDBG-86381 (PTK6)

Protein Structure

UniProt Annotation

Function

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.Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.

Subcellular Localization

Cytoplasm. Nucleus. Cell projection, ruffle. Membrane {ECO:0000250}. Note=Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate.

Disease Associations

Tissue Specificity

Epithelia-specific. Very high level in colon and high levels in small intestine and prostate, and low levels in some fetal tissues. Not expressed in breast or ovarian tissue but expressed in high percentage of breast and ovarian cancers. Also overexpressed in some metastatic melanomas, lymphomas, colon cancers, squamous cell carcinomas and prostate cancers. Also found in melanocytes. Not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform 2 is present in prostate epithelial cell lines derived from normal prostate and prostate adenocarcinomas, as well as in a variety of cell lines. {ECO:0000269PubMed:12833144, ECO:0000269PubMed:15509496, ECO:0000269PubMed:16651629, ECO:0000269PubMed:9185712}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 27 experimentally validated interaction(s) in this database.

Experimentally validated
Total	27 [view]
Protein-Protein	27 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0042802	identical protein binding

Biological Process

GO:0006468	protein phosphorylation
GO:0010976	positive regulation of neuron projection development
GO:0016477	cell migration
GO:0042503	tyrosine phosphorylation of Stat3 protein
GO:0042506	tyrosine phosphorylation of Stat5 protein
GO:0046777	protein autophosphorylation
GO:0061099	negative regulation of protein tyrosine kinase activity
GO:0071300	cellular response to retinoic acid