{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GASK1A—also referred to as Fam198a—is a secreted member of the four‐jointed protein kinase family whose function appears closely linked to the secretory pathway and caveolae biology. It is synthesized in the endoplasmic reticulum as a precursor protein and then trafficked via caveolae‐derived vesicles to the Golgi apparatus, where it undergoes proteolytic cleavage at specific arginine residues (Arg120 and Arg437) to yield its mature, secreted form. The efficiency of this maturation and secretion process depends critically on the integrity of the caveolae biogenesis pathway; in particular, key proteins such as cavin‑1 and caveolin‑1 are essential, because their absence results in retention of the Fam198a precursor in the endoplasmic reticulum and impaired secretion."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, mutations in GASK1A/Fam198a have been detected in tumors progressing during treatment with EGFR‑targeted therapies (e.g., afatinib), which suggests that altered function of this kinase may contribute to mechanisms of drug resistance. These findings, together with broader studies on secreted kinases (such as Fam20C, which regulates the phosphorylation of extracellular proteins implicated in biomineralization, lipid metabolism, cell migration, and wound healing), highlight the emerging importance of extracellular protein phosphorylation in modulating both physiological and pathological processes."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vincent S Tagliabracci, Sandra E Wiley, Xiao Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Single Kinase Generates the Majority of the Secreted Phosphoproteome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2015.05.028"}], "href": "https://doi.org/10.1016/j.cell.2015.05.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26091039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26091039"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhuang Wei, Tao Liu, Jigang Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fam198a, a member of secreted kinase, secrets through caveolae biogenesis pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biochim Biophys Sin (Shanghai) (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/abbs/gmy105"}], "href": "https://doi.org/10.1093/abbs/gmy105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30188967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30188967"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "A J van der Wekken, J L Kuiper, A Saber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overall survival in EGFR mutated non-small-cell lung cancer patients treated with afatinib after EGFR TKI and resistant mechanisms upon disease progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0182885"}], "href": "https://doi.org/10.1371/journal.pone.0182885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28854272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28854272"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Libin Liu "}, {"type": "b", "children": [{"type": "t", "text": "Lessons from cavin-1 deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Soc Trans (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BST20190380"}], "href": "https://doi.org/10.1042/BST20190380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31922193"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31922193"}]}]}]}