InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ptk6

Summary

InnateDB Protein

IDBP-214018.6

Last Modified

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

Gene Symbol

Ptk6

Protein Name

PTK6 protein tyrosine kinase 6

Synonyms

BRK; Sik; tks; Tksk;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000016511

InnateDB Gene

IDBG-214016 (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. {ECO:0000269PubMed:10913193, ECO:0000269PubMed:15471878, ECO:0000269PubMed:19501589}.

Subcellular Localization

Cytoplasm. Nucleus. Membrane. Cell projection, ruffle {ECO:0000250}. Note=Also found to be membrane- associated. Colocalizes with KHDRBS1, within the nucleus.

Disease Associations

Tissue Specificity

Expressed only in epithelial tissues, including the skin and lining of the alimentary canal. Restricted to the cell layers immediately above the proliferative cell zone in these epithelia. {ECO:0000269PubMed:15471878}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 15 interaction(s) predicted by orthology.

Experimentally validated
Total	1 [view]
Protein-Protein	1 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	15 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
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:0045926	negative regulation of growth
GO:0046777	protein autophosphorylation
GO:0060575	intestinal epithelial cell differentiation
GO:0061099	negative regulation of protein tyrosine kinase activity
GO:0071300	cellular response to retinoic acid

Cellular Component

GO:0001726	ruffle
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

MGI:99683

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011511 Variant SH3 domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM