PTK2B

Protein-coding gene in the species Homo sapiens

PTK2B

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2LK4, 3CC6, 3ET7, 3FZO, 3FZP, 3FZR, 3FZS, 3FZT, 3GM1, 3GM2, 3GM3, 3H3C, 3U3F, 4EKU, 4H1J, 4H1M, 4R32, 4XEK, 4XEF, 4XEV

Identifiers

Aliases

PTK2B, CADTK, CAKB, FADK2, FAK2, PKB, PTK, PYK2, RAFTK, protein tyrosine kinase 2 beta

External IDs

OMIM: 601212 MGI: 104908 HomoloGene: 23001 GeneCards: PTK2B

Gene location (Human)

Chr.	Chromosome 8 (human)^[1]

Band	8p21.2	Start	27,311,482 bp^[1]
Band	8p21.2	End	27,459,391 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 14 (mouse)^[2]

Band	14 D1\|14 34.36 cM	Start	66,390,706 bp^[2]
Band	14 D1\|14 34.36 cM	End	66,518,501 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

Brodmann area 10

monocyte

spleen

Brodmann area 9

bone marrow cells

lymph node

frontal pole

blood

appendix

skin of abdomen

Top expressed in

superior frontal gyrus

olfactory tubercle

piriform cortex

entorhinal cortex

hippocampus proper

subiculum

nucleus accumbens

prefrontal cortex

amygdala

cingulate gyrus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	protein-containing complex binding kinase activity signaling receptor binding ATP binding protein kinase activity non-membrane spanning protein tyrosine kinase activity transferase activity protein binding nucleotide binding 3-phosphoinositide-dependent protein kinase binding NMDA glutamate receptor activity signal transducer activity calmodulin-dependent protein kinase activity enzyme binding protein tyrosine kinase activity ubiquitin protein ligase binding protein C-terminus binding
Cellular component	membrane focal adhesion extrinsic component of cytoplasmic side of plasma membrane NMDA selective glutamate receptor complex perinuclear region of cytoplasm cytoskeleton nucleus cell projection membrane raft lamellipodium apical dendrite growth cone plasma membrane axon neuronal cell body cell cortex cell body postsynaptic density cell junction dendrite cytosol cytoplasm dendritic spine postsynapse glutamatergic synapse
Biological process	negative regulation of neuron apoptotic process cellular response to retinoic acid adaptive immune response positive regulation of actin filament polymerization tumor necrosis factor-mediated signaling pathway positive regulation of JNK cascade regulation of angiogenesis marginal zone B cell differentiation negative regulation of muscle cell apoptotic process positive regulation of translation stress fiber assembly negative regulation of ossification protein phosphorylation cell surface receptor signaling pathway vascular endothelial growth factor receptor signaling pathway regulation of cell adhesion positive regulation of reactive oxygen species metabolic process angiogenesis positive regulation of ERK1 and ERK2 cascade long-term depression positive regulation of excitatory postsynaptic potential regulation of cGMP-mediated signaling response to ethanol neuron projection development negative regulation of cell population proliferation response to cocaine apoptotic process regulation of actin cytoskeleton reorganization positive regulation of protein metabolic process epidermal growth factor receptor signaling pathway actin filament organization response to reactive oxygen species chemokine-mediated signaling pathway response to mechanical stimulus signal complex assembly bone resorption response to lithium ion response to osmotic stress positive regulation of cell growth positive regulation of nitric-oxide synthase activity positive regulation of synaptic transmission, glutamatergic ionotropic glutamate receptor signaling pathway response to organonitrogen compound positive regulation of DNA biosynthetic process positive regulation of peptidyl-tyrosine phosphorylation protein autophosphorylation innate immune response negative regulation of myeloid cell differentiation response to immobilization stress cell differentiation phosphorylation positive regulation of cell-matrix adhesion positive regulation of JUN kinase activity immune system process regulation of release of sequestered calcium ion into cytosol negative regulation of apoptotic process sprouting angiogenesis regulation of inositol trisphosphate biosynthetic process response to glucose cellular response to fluid shear stress positive regulation of angiogenesis response to calcium ion regulation of NMDA receptor activity cellular defense response oocyte maturation positive regulation of ubiquitin-dependent protein catabolic process negative regulation of potassium ion transport regulation of cell shape peptidyl-tyrosine autophosphorylation integrin-mediated signaling pathway positive regulation of B cell chemotaxis response to hormone response to cAMP regulation of nitric oxide biosynthetic process regulation of establishment of cell polarity response to hydrogen peroxide regulation of macrophage chemotaxis positive regulation of protein kinase activity regulation of leukocyte chemotaxis negative regulation of bone mineralization regulation of cell migration response to hypoxia blood vessel endothelial cell migration activation of GTPase activity positive regulation of cell migration regulation of bone mineralization positive regulation of cytosolic calcium ion concentration positive regulation of nitric oxide biosynthetic process response to stress MAPK cascade positive regulation of phosphatidylinositol 3-kinase activity positive regulation of endothelial cell migration focal adhesion assembly regulation of cell population proliferation regulation of calcium-mediated signaling positive regulation of cell population proliferation positive regulation of neuron projection development glial cell proliferation activation of Janus kinase activity peptidyl-tyrosine phosphorylation regulation of ubiquitin-dependent protein catabolic process signal transduction long-term potentiation cell adhesion interleukin-7-mediated signaling pathway interleukin-2-mediated signaling pathway regulation of synaptic plasticity protein-containing complex assembly
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


2185


19229

Ensembl


ENSG00000120899


ENSMUSG00000059456

UniProt


Q14289


Q9QVP9

RefSeq (mRNA)


NM_004103 NM_173174 NM_173175 NM_173176


NM_001162365 NM_001162366 NM_172498 NM_001360233

RefSeq (protein)


NP_004094 NP_775266 NP_775267 NP_775268


NP_001155837 NP_001155838 NP_766086 NP_001347162

Location (UCSC)

Chr 8: 27.31 – 27.46 Mb

Chr 14: 66.39 – 66.52 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the PTK2B gene.^[5]^[6]

Function

This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the MAP kinase signaling pathway. The encoded protein may represent an important signaling intermediate between neuropeptide-activated receptors or neurotransmitters that increase calcium flux and the downstream signals that regulate neuronal activity.^[7]

The encoded protein undergoes rapid tyrosine phosphorylation and activation in response to increases in the intracellular calcium concentration ^[8] , nicotinic acetylcholine receptor activation, membrane depolarization, or protein kinase C activation.^[7] In addition, SOCE-induced Pyk2 activation mediates disassembly of endothelial adherens junctions, via tyrosine (Y1981-residue) phosphorylation of VE-PTP.^[8]

This protein has been shown to bind a CRK-associated substrate, a nephrocystin, a GTPase regulator associated with FAK, and the SH2 domain of GRB2.^[7]

The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Four transcript variants encoding two different isoforms have been found for this gene.^[7]

Interactions

PTK2B has been shown to interact with:

VE-PTP^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000120899 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000059456 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J (September 1995). "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions". Nature. 376 (6543): 737–45. Bibcode:1995Natur.376..737L. doi:10.1038/376737a0. PMID 7544443. S2CID 4320927.
^ Avraham S, London R, Fu Y, Ota S, Hiregowdara D, Li J, Jiang S, Pasztor LM, White RA, Groopman JE (1995). "Identification and characterization of a novel related adhesion focal tyrosine kinase (RAFTK) from megakaryocytes and brain". J. Biol. Chem. 270 (46): 27742–51. doi:10.1074/jbc.270.46.27742. PMID 7499242.
^ ^a ^b ^c ^d "Entrez Gene: PTK2B PTK2B protein tyrosine kinase 2 beta".
^ ^a ^b ^c Soni D, Regmi SC, Wang DM, DebRoy A, Zhao YY, Vogel SM, Malik AB, Tiruppathi C (Apr 2017). "Pyk2 Phosphorylation of VE-PTP Downstream of STIM1 induced Ca2+ entry Regulates Disassembly of Adherens Junctions". American Journal of Physiology. Lung Cellular and Molecular Physiology. 312 (6): L1003–L1017. doi:10.1152/ajplung.00008.2017. PMC 5495943. PMID 28385807.
^ Manié SN, Beck AR, Astier A, Law SF, Canty T, Hirai H, Druker BJ, Avraham H, Haghayeghi N, Sattler M, Salgia R, Griffin JD, Golemis EA, Freedman AS (February 1997). "Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells". J. Biol. Chem. 272 (7): 4230–6. doi:10.1074/jbc.272.7.4230. hdl:20.500.12613/9177. PMID 9020138.
^ ^a ^b Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Dignat-George F (January 2001). "Outside-in signaling pathway linked to CD146 engagement in human endothelial cells". J. Biol. Chem. 276 (2): 1564–9. doi:10.1074/jbc.M007065200. PMID 11036077.
^ Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S, Freedman AS (January 1997). "The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to p130cas". J. Biol. Chem. 272 (1): 228–32. doi:10.1074/jbc.272.1.228. PMID 8995252.
^ ^a ^b Haglund K, Ivankovic-Dikic I, Shimokawa N, Kruh GD, Dikic I (May 2004). "Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites". J. Cell Sci. 117 (Pt 12): 2557–68. doi:10.1242/jcs.01148. PMID 15128873. S2CID 14083271.
^ Sanjay A, Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne WC, Baron R (January 2001). "Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility". J. Cell Biol. 152 (1): 181–95. doi:10.1083/jcb.152.1.181. PMC 2193648. PMID 11149930.
^ Andreev J, Simon JP, Sabatini DD, Kam J, Plowman G, Randazzo PA, Schlessinger J (March 1999). "Identification of a new Pyk2 target protein with Arf-GAP activity". Mol. Cell. Biol. 19 (3): 2338–50. doi:10.1128/MCB.19.3.2338. PMC 84026. PMID 10022920.
^ ^a ^b ^c Seabold GK, Burette A, Lim IA, Weinberg RJ, Hell JW (April 2003). "Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102". J. Biol. Chem. 278 (17): 15040–8. doi:10.1074/jbc.M212825200. PMID 12576483.
^ Felsch JS, Lane WS, Peralta EG (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. 9 (9): 485–8. Bibcode:1999CBio....9..485F. doi:10.1016/s0960-9822(99)80214-0. PMID 10322114. S2CID 15389306.
^ Ganju RK, Hatch WC, Avraham H, Ona MA, Druker B, Avraham S, Groopman JE (March 1997). "RAFTK, a novel member of the focal adhesion kinase family, is phosphorylated and associates with signaling molecules upon activation of mature T lymphocytes". J. Exp. Med. 185 (6): 1055–63. doi:10.1084/jem.185.6.1055. PMC 2196239. PMID 9091579.
^ Katagiri T, Takahashi T, Sasaki T, Nakamura S, Hattori S (June 2000). "Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402". J. Biol. Chem. 275 (26): 19645–52. doi:10.1074/jbc.M909828199. PMID 10867021.
^ Qian D, Lev S, van Oers NS, Dikic I, Schlessinger J, Weiss A (April 1997). "Tyrosine phosphorylation of Pyk2 is selectively regulated by Fyn during TCR signaling". J. Exp. Med. 185 (7): 1253–9. doi:10.1084/jem.185.7.1253. PMC 2196260. PMID 9104812.
^ Liu Y, Zhang G, Gao C, Hou X (August 2001). "NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion". Brain Res. 909 (1–2): 51–8. doi:10.1016/s0006-8993(01)02619-1. PMID 11478920. S2CID 21062909.
^ Wang Q, Xie Y, Du QS, Wu XJ, Feng X, Mei L, McDonald JM, Xiong WC (February 2003). "Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin". J. Cell Biol. 160 (4): 565–75. doi:10.1083/jcb.200207036. PMC 2173747. PMID 12578912.
^ Benzing T, Gerke P, Höpker K, Hildebrandt F, Kim E, Walz G (August 2001). "Nephrocystin interacts with Pyk2, p130(Cas), and tensin and triggers phosphorylation of Pyk2". Proc. Natl. Acad. Sci. U.S.A. 98 (17): 9784–9. Bibcode:2001PNAS...98.9784B. doi:10.1073/pnas.171269898. PMC 55530. PMID 11493697.
^ Lev S, Hernandez J, Martinez R, Chen A, Plowman G, Schlessinger J (March 1999). "Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein". Mol. Cell. Biol. 19 (3): 2278–88. doi:10.1128/mcb.19.3.2278. PMC 84020. PMID 10022914.
^ Chauhan D, Pandey P, Hideshima T, Treon S, Raje N, Davies FE, Shima Y, Tai YT, Rosen S, Avraham S, Kharbanda S, Anderson KC (September 2000). "SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells". J. Biol. Chem. 275 (36): 27845–50. doi:10.1074/jbc.M003428200. PMID 10880513.
^ Ganju RK, Brubaker SA, Chernock RD, Avraham S, Groopman JE (June 2000). "Beta-chemokine receptor CCR5 signals through SHP1, SHP2, and Syk". J. Biol. Chem. 275 (23): 17263–8. doi:10.1074/jbc.M000689200. PMID 10747947.
^ ^a ^b Kumar S, Avraham S, Bharti A, Goyal J, Pandey P, Kharbanda S (October 1999). "Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1". J. Biol. Chem. 274 (43): 30657–63. doi:10.1074/jbc.274.43.30657. PMID 10521452.
^ ^a ^b Matsuya M, Sasaki H, Aoto H, Mitaka T, Nagura K, Ohba T, Ishino M, Takahashi S, Suzuki R, Sasaki T (January 1998). "Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions". J. Biol. Chem. 273 (2): 1003–14. doi:10.1074/jbc.273.2.1003. PMID 9422762.
^ Hiregowdara D, Avraham H, Fu Y, London R, Avraham S (April 1997). "Tyrosine phosphorylation of the related adhesion focal tyrosine kinase in megakaryocytes upon stem cell factor and phorbol myristate acetate stimulation and its association with paxillin". J. Biol. Chem. 272 (16): 10804–10. doi:10.1074/jbc.272.16.10804. PMID 9099734.
^ Chow A, Davis AJ, Gawler DJ (March 2000). "Identification of a novel protein complex containing annexin VI, Fyn, Pyk2, and the p120(GAP) C2 domain". FEBS Lett. 469 (1): 88–92. doi:10.1016/s0014-5793(00)01252-7. PMID 10708762. S2CID 21394463.
^ Zrihan-Licht S, Fu Y, Settleman J, Schinkmann K, Shaw L, Keydar I, Avraham S, Avraham H (March 2000). "RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion". Oncogene. 19 (10): 1318–28. doi:10.1038/sj.onc.1203422. PMID 10713673.
^ Ueda H, Abbi S, Zheng C, Guan JL (April 2000). "Suppression of Pyk2 kinase and cellular activities by FIP200". J. Cell Biol. 149 (2): 423–30. doi:10.1083/jcb.149.2.423. PMC 2175150. PMID 10769033.
^ Keely SJ, Calandrella SO, Barrett KE (April 2000). "Carbachol-stimulated transactivation of epidermal growth factor receptor and mitogen-activated protein kinase in T(84) cells is mediated by intracellular Ca2+, PYK-2, and p60(src)". J. Biol. Chem. 275 (17): 12619–25. doi:10.1074/jbc.275.17.12619. PMID 10777553.
^ Dikic I, Tokiwa G, Lev S, Courtneidge SA, Schlessinger J (October 1996). "A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation". Nature. 383 (6600): 547–50. Bibcode:1996Natur.383..547D. doi:10.1038/383547a0. PMID 8849729. S2CID 4328514.
^ Wang X, Yang Y, Guo X, Sampson ER, Hsu CL, Tsai MY, Yeh S, Wu G, Guo Y, Chang C (May 2002). "Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator". J. Biol. Chem. 277 (18): 15426–31. doi:10.1074/jbc.M111218200. PMID 11856738.
^ Thomas SM, Hagel M, Turner CE (January 1999). "Characterization of a focal adhesion protein, Hic-5, that shares extensive homology with paxillin". J. Cell Sci. 112 (2): 181–90. doi:10.1242/jcs.112.2.181. PMID 9858471.

External links

Overview of all the structural information available in the PDB for UniProt: Q14289 (Protein-tyrosine kinase 2-beta) at the PDBe-KB.

Protein kinases: tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4
Insulin receptor family	IGF1R INSR INSRR
PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)
FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4
VEGF receptors family	VEGFR1 VEGFR2 VEGFR3
HGF receptor family	MET RON
Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

ROR1
ROR2

DDR receptor family

DDR1
DDR2

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AATYK
AATYK2

AXL receptor family

RET receptor family

uncategorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG
ACK family	ACK1 TNK1
CSK family	CSK MATK
FAK family	FAK PYK2
FES family	FES FER
FRK family	FRK BRK SRMS
JAK family	JAK1 JAK2 JAK3 TYK2
SRC-A family	SRC FGR FYN YES1
SRC-B family	BLK HCK LCK LYN
TEC family	TEC BMX BTK ITK TXK
SYK family	SYK ZAP70

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)