{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTNK2 (also known as ACK1) is a non‐receptor tyrosine kinase that functions as a central integrator of signals from activated receptor tyrosine kinases and growth factor receptors. In several cancer models—including prostate, breast and other tumors—TNK2 becomes activated to phosphorylate key downstream substrates such as the androgen receptor and AKT. This activity promotes androgen‐independent gene transcription, cell survival and rapid tumor progression, contributing to therapy resistance and poor clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutational and structural analyses have further revealed that TNK2/ACK1 activity is modulated by point mutations, gene amplification and post‐translational modifications that enhance its autophosphorylation and kinase output. For example, alterations that disrupt its interactions with ubiquitin ligases or modify critical tyrosine residues contribute to increased binding to effectors such as Cdc42 and p130Cas, thereby potentiating cell proliferation, migration and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in promoting oncogenic signaling, TNK2 is a key regulator of receptor trafficking and endocytosis. It associates with components of the endocytic machinery—modulating epidermal growth factor receptor (EGFR) turnover and engaging autophagy‐related proteins—to control the duration and intensity of receptor-mediated signaling. Such regulation, including the interplay with ubiquitin ligases and actin‐nucleating factors, influences downstream pathways that affect cell growth and therapeutic sensitivity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these canonical roles in tumorigenesis and receptor turnover, TNK2 exerts pleiotropic effects in other biological contexts. It has been implicated in modulating signaling pathways in hematologic malignancies, influencing immune cell activation and T‐cell receptor signaling, altering viral entry mechanisms and even affecting neural differentiation. Moreover, its dysregulation frequently correlates with metastatic behavior and serves as an independent prognostic marker in several cancers, highlighting its potential as an actionable therapeutic target to overcome resistance to conventional treatments."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nupam P Mahajan, Yuanbo Liu, Samarpan Majumder, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M806877200"}], "href": "https://doi.org/10.1074/jbc.M806877200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19144635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19144635"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Boon Tin Chua, Shu Jing Lim, Su Chin Tham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic mutation in the ACK1 ubiquitin association domain enhances oncogenic signaling through EGFR regulation in renal cancer derived cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molonc.2010.03.001"}], "href": "https://doi.org/10.1016/j.molonc.2010.03.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20359967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20359967"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Kiran Mahajan, Domenico Coppola, Y Ann Chen, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M604342200"}], "href": "https://doi.org/10.1074/jbc.M604342200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17038317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17038317"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jillian Howlin, Jeanette Rosenkvist, Tommy Andersson "}, {"type": "b", "children": [{"type": "t", "text": "TNK2 preserves epidermal growth factor receptor expression on the cell surface and enhances migration and invasion of human breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/bcr2087"}], "href": "https://doi.org/10.1186/bcr2087"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18435854"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18435854"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Kiran Mahajan, Harshani R Lawrence, Nicholas J Lawrence, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Comparison of gene expression profiles between primary tumor and metastatic lesions in gastric cancer patients using laser microdissection and cDNA microarray."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Gastroenterol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3748/wjg.v12.i43.6949"}], "href": "https://doi.org/10.3748/wjg.v12.i43.6949"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17109515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17109515"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Julie C Lougheed, Rui-Hong Chen, Polly Mak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406703200"}], "href": "https://doi.org/10.1074/jbc.M406703200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15308621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15308621"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Daniel S W Tan, Benjamin Haaland, Jia Min Gan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bosutinib inhibits migration and invasion via ACK1 in KRAS mutant non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1476-4598-13-13"}], "href": "https://doi.org/10.1186/1476-4598-13-13"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24461128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24461128"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jiannan Zhang, Tao Chen, Qin Mao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDGFR-β-activated ACK1-AKT signaling promotes glioma tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.29234"}], "href": "https://doi.org/10.1002/ijc.29234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25257795"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25257795"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Binhui Xie, Qinshan Zen, Xiaonong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2015.2910"}], "href": "https://doi.org/10.3892/ijo.2015.2910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25738261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25738261"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Chandra Childress, Qiong Lin, Wannian Yang "}, {"type": "b", "children": [{"type": "t", "text": "Dimerization is required for SH3PX1 tyrosine phosphorylation in response to epidermal growth factor signalling and interaction with ACK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20050576"}], "href": "https://doi.org/10.1042/BJ20050576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16316319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16316319"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Lene Melsaether Grøvdal, Lene E Johannessen, Marianne Skeie Rødland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of Ack1 inhibits down-regulation of the EGF receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.12.017"}], "href": "https://doi.org/10.1016/j.yexcr.2007.12.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18262180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18262180"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Lin Pao-Chun, Perry M Chan, Wing Chan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.072660"}], "href": "https://doi.org/10.1074/jbc.M109.072660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19815557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19815557"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Nisintha Mahendrarajah, Marina E Borisova, Sigrid Reichardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSP90 is necessary for the ACK1-dependent phosphorylation of STAT1 and STAT3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2017.07.014"}], "href": "https://doi.org/10.1016/j.cellsig.2017.07.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28739485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28739485"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Sylwia Jones, Debbie L Cunningham, Joshua Z Rappoport, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The non-receptor tyrosine kinase Ack1 regulates the fate of activated EGFR by inducing trafficking to the p62/NBR1 pre-autophagosome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.136895"}], "href": "https://doi.org/10.1242/jcs.136895"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24413169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24413169"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Laura C Kelley, Scott A Weed "}, {"type": "b", "children": [{"type": "t", "text": "Cortactin is a substrate of activated Cdc42-associated kinase 1 (ACK1) during ligand-induced epidermal growth factor receptor downregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0044363"}], "href": "https://doi.org/10.1371/journal.pone.0044363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22952966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22952966"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Julia E Maxson, Melissa L Abel, Jinhua Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-15-0817"}], "href": "https://doi.org/10.1158/0008-5472.CAN-15-0817"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26677978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26677978"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Kazuya Shinmura, Shinichiro Kiyose, Kiyoko Nagura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Surg Oncol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jso.23482"}], "href": "https://doi.org/10.1002/jso.23482"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24178904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24178904"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Song-Hui Xu, Jin-Zhou Huang, Min Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Amplification of ACK1 promotes gastric tumorigenesis via ECD-dependent p53 ubiquitination degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6194"}], "href": "https://doi.org/10.18632/oncotarget.6194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26498357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26498357"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Hongbing Jiang, Christian Leung, Stephen Tahan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL, and NCK1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.50276"}], "href": "https://doi.org/10.7554/eLife.50276"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31769754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31769754"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Zhenyu Ji, Ching-Ni Njauw, Samantha Guhan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of ACK1 Upregulates EGFR and Mediates Resistance to BRAF Inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2020.06.041"}], "href": "https://doi.org/10.1016/j.jid.2020.06.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33159968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33159968"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "George J N Tetley, Helen R Mott, R Neil Cooley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A dock and coalesce mechanism driven by hydrophobic interactions governs Cdc42 binding with its effector protein ACK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M117.789883"}], "href": "https://doi.org/10.1074/jbc.M117.789883"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28539360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28539360"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Lorraine Eley, Shabbir H Moochhala, Roslyn Simms, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nephrocystin-1 interacts directly with Ack1 and is expressed in human collecting duct."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2008.05.016"}], "href": "https://doi.org/10.1016/j.bbrc.2008.05.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18477472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18477472"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yoshifumi Fujimoto, Hidenori Ochi, Toshiro Maekawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A single nucleotide polymorphism in activated Cdc42 associated tyrosine kinase 1 influences the interferon therapy in hepatitis C patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2010.07.021"}], "href": "https://doi.org/10.1016/j.jhep.2010.07.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129804"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Nupam P Mahajan, Domenico Coppola, Jongphil Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blockade of ACK1/TNK2 To Squelch the Survival of Prostate Cancer Stem-like Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-20172-z"}], "href": "https://doi.org/10.1038/s41598-018-20172-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29386546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29386546"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Youg R Thaker, Asha Recino, Monika Raab, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.759555"}], "href": "https://doi.org/10.1074/jbc.M116.759555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28188290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28188290"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Jinhong Zhu, Yang Liu, Meng Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of downstream signaling cascades of ACK1 and prognostic classifiers in non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.202408"}], "href": "https://doi.org/10.18632/aging.202408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33495411"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33495411"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Wing Chan, Soon-Tuck Sit, Ed Manser "}, {"type": "b", "children": [{"type": "t", "text": "The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20102156"}], "href": "https://doi.org/10.1042/BJ20102156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21309750"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21309750"}]}]}]}