Tyrosine Kinase, Non Receptor 2 (TNK2)

ACK; ACK1; Activated CDC42 Associated Kinase 1

SPN	U060
HGNC	19297
MGI	1858308
PubMed	18435854
RGD	1305957
UniProt	Q07912
Wiki	TNK2

Activated CDC42 kinase 1 is a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain.

The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.

Reference

"A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42."
Nature 363:364-367(1993) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence, annotation and analysis of human chromosome 3."
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas."
Nat. Cell Biol. 1:507-513(1999) [PubMed] [Europe PMC] [Abstract]

"Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent tyrosine phosphorylation."
Biochem. Biophys. Res. Commun. 268:141-147(2000) [PubMed] [Europe PMC] [Abstract]

"The tyrosine kinase ACK1 associates with clathrin-coated vesicles through a binding motif shared by arrestin and other adaptors."
J. Biol. Chem. 276:18392-18398(2001) [PubMed] [Europe PMC] [Abstract]

"Cdc42-dependent nuclear translocation of non-receptor tyrosine kinase, ACK."
Biochem. Biophys. Res. Commun. 314:571-579(2004) [PubMed] [Europe PMC] [Abstract]

"Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox."
Cancer Res. 65:10514-10523(2005) [PubMed] [Europe PMC] [Abstract]

"SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1."
FEBS Lett. 579:5040-5048(2005) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase."
J. Biol. Chem. 280:42219-42226(2005) [PubMed] [Europe PMC] [Abstract]

"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]

"Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1."
Proc. Natl. Acad. Sci. U.S.A. 102:15901-15906(2005) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas."
J. Biol. Chem. 281:37527-37535(2006) [PubMed] [Europe PMC] [Abstract]

"Purification and enzyme activity of ACK1."
Methods Enzymol. 406:250-260(2006) [PubMed] [Europe PMC] [Abstract]

"Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 104:8438-8443(2007) [PubMed] [Europe PMC] [Abstract]

"Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct."
Biochem. Biophys. Res. Commun. 371:877-882(2008) [PubMed] [Europe PMC] [Abstract]

"TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells."
Breast Cancer Res. 10:R36-R36(2008) [PubMed] [Europe PMC] [Abstract]

"Dysregulation of Ack1 inhibits down-regulation of the EGF receptor."
Exp. Cell Res. 314:1292-1300(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2."
J. Biol. Chem. 284:8185-8194(2009) [PubMed] [Europe PMC] [Abstract]

"Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling."
J. Biol. Chem. 284:34954-34963(2009) [PubMed] [Europe PMC] [Abstract]

"Large-scale proteomics analysis of the human kinome."
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]

"Regulation of Ack1 localization and activity by the amino-terminal SAM domain."
BMC Biochem. 11:42-42(2010) [PubMed] [Europe PMC] [Abstract]

"Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases."
Oncogene 29:3208-3216(2010) [PubMed] [Europe PMC] [Abstract]

"Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation."
PLoS ONE 5:E9646-E9646(2010) [PubMed] [Europe PMC] [Abstract]

"Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity."
Prostate 70:1274-1285(2010) [PubMed] [Europe PMC] [Abstract]

"The Cdc42-associated kinase ACK1 is not auto-inhibited but requires Src for activation."
Biochem. J. 435:355-364(2011) [PubMed] [Europe PMC] [Abstract]

"Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at arrested endocytic clathrin-coated pits of cells that lack dynamin."
Mol. Biol. Cell 22:493-502(2011) [PubMed] [Europe PMC] [Abstract]

"Shepherding AKT and androgen receptor by Ack1 tyrosine kinase."
J. Cell. Physiol. 224:327-333(2010) [PubMed] [Europe PMC] [Abstract]

"Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK."
Nature 399:384-388(1999) [PubMed] [Europe PMC] [Abstract]

"Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1."
J. Biol. Chem. 279:44039-44045(2004) [PubMed] [Europe PMC] [Abstract]

"Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors."
Bioorg. Med. Chem. Lett. 18:6352-6356(2008) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]