Signaling by PTK6

Peng M, Ball-Kell SM, Tyner AL. Protein tyrosine kinase 6 promotes ERBB2-induced mammary gland tumorigenesis in the mouse. Cell Death & Disease. 2015 Aug 06;6(8):e1848. doi: 10.1038/cddis.2015.210.; Goel RK, Lukong KE. Tracing the footprints of the breast cancer oncogene BRK — Past till present. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2015 Aug;1856(1):39–54. doi: 10.1016/j.bbcan.2015.05.001.; Fan G, Aleem S, Yang M, Miller WT, Tonks NK. Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase*. Journal of Biological Chemistry. 2015 Jun;290(26):15934–47. doi: 10.1074/jbc.m115.651703.; Patel P, Asbach B, Shteyn E, Gomez C, Coltoff A, Bhuyan S, Tyner AL, Wagner R, Blain SW. Brk/Protein Tyrosine Kinase 6 Phosphorylates p27 KIP1 , Regulating the Activity of Cyclin D–Cyclin-Dependent Kinase 4. Molecular and Cellular Biology. 2015 May 01;35(9):1506–22. doi: 10.1128/mcb.01206-14.; Pires IM, Blokland NJ, Broos AW, Poujade FA, Senra JM, Eccles SA, Span PN, Harvey AJ, Hammond EM. HIF-1a-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion. Cancer Biol Ther. 2014 Oct;15(10):1350–7. PMID: 25019382; PMCID: PMC4130728.; Ono H, Basson MD, Ito H. PTK6 Promotes Cancer Migration and Invasion in Pancreatic Cancer Cells Dependent on ERK Signaling. PLoS ONE. 2014 May 01;9(5):e96060. doi: 10.1371/journal.pone.0096060.; Regan Anderson TM, Peacock DL, Daniel AR, Hubbard GK, Lofgren KA, Girard BJ, Schörg A, Hoogewijs D, Wenger RH, Seagroves TN, Lange CA. Breast tumor kinase (Brk/PTK6) is a mediator of hypoxia-associated breast cancer progression. Cancer Res. 2013 Sep 15;73(18):5810–20. PMID: 23928995; PMCID: PMC3820501.; Fan G, Lin G, Lucito R, Tonks NK. Protein-tyrosine Phosphatase 1B Antagonized Signaling by Insulin-like Growth Factor-1 Receptor and Kinase BRK/PTK6 in Ovarian Cancer Cells*. Journal of Biological Chemistry. 2013 Aug;288(34):24923–34. doi: 10.1074/jbc.m113.482737.; Kang S, Lee S. PTK6 promotes degradation of c-Cbl through PTK6-mediated phosphorylation. Biochemical and Biophysical Research Communications. 2013 Feb;431(4):734–9. doi: 10.1016/j.bbrc.2013.01.046.; Gao Y, Cimica V, Reich NC. Suppressor of Cytokine Signaling 3 Inhibits Breast Tumor Kinase Activation of STAT3. Journal of Biological Chemistry. 2012 Jun;287(25):20904–12. doi: 10.1074/jbc.m111.334144.; Li X, Lu Y, Liang K, Hsu JM, Albarracin C, Mills GB, Hung MC, Fan Z. Brk/PTK6 sustains activated EGFR signaling through inhibiting EGFR degradation and transactivating EGFR. Oncogene. 2012 Oct 04;31(40):4372–83. PMID: 22231447; PMCID: PMC3326223.; Zheng Y, Asara JM, Tyner AL. Protein-tyrosine Kinase 6 Promotes Peripheral Adhesion Complex Formation and Cell Migration by Phosphorylating p130 CRK-associated Substrate. Journal of Biological Chemistry. 2012 Jan;287(1):148–58. doi: 10.1074/jbc.m111.298117.; Tanizaki J, Okamoto I, Sakai K, Nakagawa K. Differential roles of trans-phosphorylated EGFR, HER2, HER3, and RET as heterodimerisation partners of MET in lung cancer with MET amplification. British Journal of Cancer. 2011 Aug 16;105(6):807–13. doi: 10.1038/bjc.2011.322.; Ikeda O, Mizushima A, Sekine Y, Yamamoto C, Muromoto R, Nanbo A, Oritani K, Yoshimura A, Matsuda T. Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells. Cancer Sci. 2011 Apr;102(4):756–61. doi: 10.1111/j.1349-7006.2010.01842.x. PMID: 21205088.; Ikeda O, Sekine Y, Mizushima A, Nakasuji M, Miyasaka Y, Yamamoto C, Muromoto R, Nanbo A, Oritani K, Yoshimura A, Matsuda T. Interactions of STAP-2 with Brk and STAT3 Participate in Cell Growth of Human Breast Cancer Cells. Journal of Biological Chemistry. 2010 Dec;285(49):38093–103. doi: 10.1074/jbc.m110.162388.; Zheng Y, Peng M, Wang Z, Asara JM, Tyner AL. Protein Tyrosine Kinase 6 Directly Phosphorylates AKT and Promotes AKT Activation in Response to Epidermal Growth Factor. Molecular and Cellular Biology. 2010 Sep 01;30(17):4280–92. doi: 10.1128/mcb.00024-10.; Kang S, Lee E, Yoon H, Randazzo PA, Lee S. PTK6 Inhibits Down-regulation of EGF Receptor through Phosphorylation of ARAP1. Journal of Biological Chemistry. 2010 Aug;285(34):26013–21. doi: 10.1074/jbc.m109.088971.; Castro NE, Lange CA. Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells. Breast Cancer Res. 2010;12(4):R60. PMID: 20687930; PMCID: PMC2949652.; Lukong KE, Huot ME, Richard S. BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest. Cell Signal. 2009 Sep;21(9):1415–22. doi: 10.1016/j.cellsig.2009.04.008. PMID: 19439179.; Ikeda O, Miyasaka Y, Sekine Y, Mizushima A, Muromoto R, Nanbo A, Yoshimura A, Matsuda T. STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation. Biochemical and Biophysical Research Communications. 2009 Jun;384(1):71–5. doi: 10.1016/j.bbrc.2009.04.076.; Shen CH, Chen HY, Lin MS, Li FY, Chang CC, Kuo ML, Settleman J, Chen RH. Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and promote breast carcinoma growth, migration, and invasion. Cancer Res. 2008 Oct 01;68(19):7779–87. doi: 10.1158/0008-5472.can-08-0997. PMID: 18829532.; Xiang B, Chatti K, Qiu H, Lakshmi B, Krasnitz A, Hicks J, Yu M, Miller WT, Muthuswamy SK. Brk is coamplified with ErbB2 to promote proliferation in breast cancer. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12463–8. PMID: 18719096; PMCID: PMC2527934.; Lukong KE, Richard S. Breast tumor kinase BRK requires kinesin-2 subunit KAP3A in modulation of cell migration. Cell Signal. 2008 Feb;20(2):432–42. doi: 10.1016/j.cellsig.2007.11.003. PMID: 18077133.; Chakraborty G, Jain S, Kundu GC. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res. 2008 Jan 01;68(1):152–61. doi: 10.1158/0008-5472.can-07-2126. PMID: 18172307.; Ostrander JH, Daniel AR, Lofgren K, Kleer CG, Lange CA. Breast tumor kinase (protein tyrosine kinase 6) regulates heregulin-induced activation of ERK5 and p38 MAP kinases in breast cancer cells. Cancer Res. 2007 May 01;67(9):4199–209. doi: 10.1158/0008-5472.can-06-3409. PMID: 17483331.; Lukong KE, Larocque D, Tyner AL, Richard S. Tyrosine Phosphorylation of Sam68 by Breast Tumor Kinase Regulates Intranuclear Localization and Cell Cycle Progression. Journal of Biological Chemistry. 2005 Nov;280(46):38639–47. doi: 10.1074/jbc.m505802200.; Zhang P, Ostrander JH, Faivre EJ, Olsen A, Fitzsimmons D, Lange CA. Regulated Association of Protein Kinase B/Akt with Breast Tumor Kinase. Journal of Biological Chemistry. 2005 Jan;280(3):1982–91. doi: 10.1074/jbc.m412038200.; Haegebarth A, Heap D, Bie W, Derry JJ, Richard S, Tyner AL. The Nuclear Tyrosine Kinase BRK/Sik Phosphorylates and Inhibits the RNA-binding Activities of the Sam68-like Mammalian Proteins SLM-1 and SLM-2. Journal of Biological Chemistry. 2004 Dec;279(52):54398–404. doi: 10.1074/jbc.m409579200.; Chen H, Shen C, Tsai Y, Lin F, Huang Y, Chen R. Brk Activates Rac1 and Promotes Cell Migration and Invasion by Phosphorylating Paxillin. Molecular and Cellular Biology. 2004 Dec 01;24(24):10558–72. doi: 10.1128/mcb.24.24.10558-10572.2004.; Kamalati T, Jolin HE, Fry MJ, Crompton MR. Expression of the BRK tyrosine kinase in mammary epithelial cells enhances the coupling of EGF signalling to PI 3-kinase and Akt, via erbB3 phosphorylation. Oncogene. 2000 Nov 16;19(48):5471–6. doi: 10.1038/sj.onc.1203931. PMID: 11114724.; Derry JJ, Richard S, Valderrama Carvajal H, Ye X, Vasioukhin V, Cochrane AW, Chen T, Tyner AL. Sik (BRK) Phosphorylates Sam68 in the Nucleus and Negatively Regulates Its RNA Binding Ability. Molecular and Cellular Biology. 2000 Aug 01;20(16):6114–26. doi: 10.1128/mcb.20.16.6114-6126.2000.; Kamalati T, Jolin HE, Mitchell PJ, Barker KT, Jackson LE, Dean CJ, Page MJ, Gusterson BA, Crompton MR. Brk, a Breast Tumor-derived Non-receptor Protein-tyrosine Kinase, Sensitizes Mammary Epithelial Cells to Epidermal Growth Factor. Journal of Biological Chemistry. 1996 Nov;271(48):30956–63. doi: 10.1074/jbc.271.48.30956.

Metabolites

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

GTP(4-)

Formula: C10H12N5O14P3 (518.9593642)

CAS ID: 86527-72-2

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
3.6.5.-
2.3.2.27 RING-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
2.7.10.1 receptor protein-tyrosine kinase ATP:[protein]-L-tyrosine O-phosphotransferase (receptor-type)
2.7.10.2 non-specific protein-tyrosine kinase ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific)
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
3.1.3.48 protein-tyrosine-phosphatase protein-tyrosine-phosphate phosphohydrolase
3.6.5.2 small monomeric GTPase GTP phosphohydrolase (cell-regulating)


Proteins

Protein ID name full name