InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Ptk2b

Summary

InnateDB Protein

IDBP-175128.6

Last Modified

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

Gene Symbol

Ptk2b

Protein Name

PTK2 protein tyrosine kinase 2 beta

Synonyms

CADTK; CAKB; CAKbeta; E430023O05Rik; FADK2; FAK2; PYK2; Raftk;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000022622

InnateDB Gene

IDBG-175126 (Ptk2b)

Protein Structure

UniProt Annotation

Function

Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T- cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376' (By similarity). Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2 (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm. Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, focal adhesion. Cell projection, lamellipodium {ECO:0000250}. Cytoplasm, cell cortex {ECO:0000250}. Nucleus {ECO:0000250}. Note=Colocalizes with integrins at the cell periphery (By similarity). Interaction with NPHP1 induces the membrane-association of the kinase. Colocalizes with PXN at the microtubule-organizing center. The tyrosine phosphorylated form is detected at cell-cell contacts. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 73 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	20 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	73 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004683	calmodulin-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0004871	signal transducer activity
GO:0004972	N-methyl-D-aspartate selective glutamate receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0032403	protein complex binding
GO:0043423	3-phosphoinositide-dependent protein kinase binding

Biological Process

GO:0000165	MAPK cascade
GO:0001556	oocyte maturation
GO:0001666	response to hypoxia
GO:0001954	positive regulation of cell-matrix adhesion
GO:0002040	sprouting angiogenesis
GO:0002315	marginal zone B cell differentiation
GO:0006468	protein phosphorylation
GO:0006968	cellular defense response
GO:0006970	response to osmotic stress
GO:0007166	cell surface receptor signaling pathway
GO:0007172	signal complex assembly
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007229	integrin-mediated signaling pathway
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0008360	regulation of cell shape
GO:0009612	response to mechanical stimulus
GO:0009725	response to hormone
GO:0009749	response to glucose
GO:0010226	response to lithium ion
GO:0010595	positive regulation of endothelial cell migration
GO:0010656	negative regulation of muscle cell apoptotic process
GO:0010752	regulation of cGMP-mediated signaling
GO:0010758	regulation of macrophage chemotaxis
GO:0010976	positive regulation of neuron projection development
GO:0014009	glial cell proliferation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030155	regulation of cell adhesion
GO:0030307	positive regulation of cell growth
GO:0030502	negative regulation of bone mineralization
GO:0030826	regulation of cGMP biosynthetic process
GO:0030838	positive regulation of actin filament polymerization
GO:0031175	neuron projection development
GO:0032863	activation of Rac GTPase activity
GO:0032960	regulation of inositol trisphosphate biosynthetic process
GO:0033209	tumor necrosis factor-mediated signaling pathway
GO:0035235	ionotropic glutamate receptor signaling pathway
GO:0038083	peptidyl-tyrosine autophosphorylation
GO:0042220	response to cocaine
GO:0042493	response to drug
GO:0042542	response to hydrogen peroxide
GO:0042976	activation of Janus kinase activity
GO:0043066	negative regulation of apoptotic process
GO:0043149	stress fiber assembly
GO:0043267	negative regulation of potassium ion transport
GO:0043507	positive regulation of JUN kinase activity
GO:0043524	negative regulation of neuron apoptotic process
GO:0043534	blood vessel endothelial cell migration
GO:0043552	positive regulation of phosphatidylinositol 3-kinase activity
GO:0045428	regulation of nitric oxide biosynthetic process
GO:0045453	bone resorption
GO:0045471	response to ethanol
GO:0045638	negative regulation of myeloid cell differentiation
GO:0045727	positive regulation of translation
GO:0045766	positive regulation of angiogenesis
GO:0045860	positive regulation of protein kinase activity
GO:0046330	positive regulation of JNK cascade
GO:0048010	vascular endothelial growth factor receptor signaling pathway
GO:0048041	focal adhesion assembly
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0050848	regulation of calcium-mediated signaling
GO:0051000	positive regulation of nitric-oxide synthase activity
GO:0051279	regulation of release of sequestered calcium ion into cytosol
GO:0051591	response to cAMP
GO:0051592	response to calcium ion
GO:0051968	positive regulation of synaptic transmission, glutamatergic
GO:0060291	long-term synaptic potentiation
GO:0070098	chemokine-mediated signaling pathway
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0071300	cellular response to retinoic acid
GO:2000060	positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000114	regulation of establishment of cell polarity
GO:2000249	regulation of actin cytoskeleton reorganization
GO:2000310	regulation of N-methyl-D-aspartate selective glutamate receptor activity
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2000463	positive regulation of excitatory postsynaptic membrane potential
GO:2000538	positive regulation of B cell chemotaxis

Cellular Component

GO:0005634	nucleus
GO:0005856	cytoskeleton
GO:0005925	focal adhesion
GO:0005938	cell cortex
GO:0014069	postsynaptic density
GO:0017146	N-methyl-D-aspartate selective glutamate receptor complex
GO:0030027	lamellipodium
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone
GO:0043025	neuronal cell body
GO:0044297	cell body
GO:0045121	membrane raft
GO:0048471	perinuclear region of cytoplasm
GO:0097440	apical dendrite

Protein Structure and Domains

PDB ID

MGI:104908

InterPro

IPR000299 FERM domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR005189 Focal adhesion kinase, targeting (FAT) domain
IPR011009 Protein kinase-like domain
IPR019748 FERM central domain
IPR019749 Band 4.1 domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR029071 Ubiquitin-related domain

PFAM

PF00069
PF07714
PF03623
PF00373

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00295
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt