دورية أكاديمية

The Evolution of Duplicated Genes of the Cpi-17/Phi-1 ( ppp1r14 ) Family of Protein Phosphatase 1 Inhibitors in Teleosts.

التفاصيل البيبلوغرافية
العنوان: The Evolution of Duplicated Genes of the Cpi-17/Phi-1 ( ppp1r14 ) Family of Protein Phosphatase 1 Inhibitors in Teleosts.
المؤلفون: Lang I; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Virk G; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Zheng DC; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Young J; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Nguyen MJ; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Amiri R; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Fong M; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Arata A; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA., Chadaideh KS; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA.; Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA., Walsh S; Life Sciences, Soka University of America, Aliso Viejo, CA 92656, USA., Weiser DC; Department of Biological Sciences, University of the Pacific, Stockton, CA 98211, USA.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2020 Aug 09; Vol. 21 (16). Date of Electronic Publication: 2020 Aug 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Fish Proteins/*genetics , Genes, Duplicate/*genetics , Intracellular Signaling Peptides and Proteins/*genetics , Muscle Proteins/*genetics , Proteins/*genetics, Amino Acid Sequence ; Animals ; Embryo, Nonmammalian/embryology ; Embryo, Nonmammalian/metabolism ; Evolution, Molecular ; Fish Proteins/classification ; Fish Proteins/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; HEK293 Cells ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins/classification ; Intracellular Signaling Peptides and Proteins/metabolism ; Muscle Proteins/classification ; Muscle Proteins/metabolism ; Phosphoprotein Phosphatases/classification ; Phosphoprotein Phosphatases/genetics ; Phosphoprotein Phosphatases/metabolism ; Phylogeny ; Proteins/classification ; Proteins/metabolism ; Sequence Homology, Amino Acid ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish/metabolism
مستخلص: The Cpi-17 ( ppp1r14 ) gene family is an evolutionarily conserved, vertebrate specific group of protein phosphatase 1 (PP1) inhibitors. When phosphorylated, Cpi-17 is a potent inhibitor of myosin phosphatase (MP), a holoenzyme complex of the regulatory subunit Mypt1 and the catalytic subunit PP1. Myosin phosphatase dephosphorylates the regulatory myosin light chain (Mlc2) and promotes actomyosin relaxation, which in turn, regulates numerous cellular processes including smooth muscle contraction, cytokinesis, cell motility, and tumor cell invasion. We analyzed zebrafish homologs of the Cpi-17 family, to better understand the mechanisms of myosin phosphatase regulation. We found single homologs of both Kepi ( ppp1r14c ) and Gbpi ( ppp1r14d ) in silico, but we detected no expression of these genes during early embryonic development. Cpi-17 ( ppp1r14a ) and Phi-1 ( ppp1r14b ) each had two duplicate paralogs, ( ppp1r14aa and ppp1r14ab ) and ( ppp1r14ba and ppp1r14bb ), which were each expressed during early development. The spatial expression pattern of these genes has diverged, with ppp1r14aa and ppp1r14bb expressed primarily in smooth muscle and skeletal muscle, respectively, while ppp1r14ab and ppp1r14ba are primarily expressed in neural tissue. We observed that, in in vitro and heterologous cellular systems, the Cpi-17 paralogs both acted as potent myosin phosphatase inhibitors, and were indistinguishable from one another. In contrast, the two Phi-1 paralogs displayed weak myosin phosphatase inhibitory activity in vitro, and did not alter myosin phosphorylation in cells. Through deletion and chimeric analysis, we identified that the difference in specificity for myosin phosphatase between Cpi-17 and Phi-1 was encoded by the highly conserved PHIN (phosphatase holoenzyme inhibitory) domain, and not the more divergent N- and C- termini. We also showed that either Cpi-17 paralog can rescue the knockdown phenotype, but neither Phi-1 paralog could do so. Thus, we provide new evidence about the biochemical and developmental distinctions of the zebrafish Cpi-17 protein family.
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معلومات مُعتمدة: R15 GM124601 United States GM NIGMS NIH HHS; IOS-1121310 National Science Foundation; R15GM124601 National Institute of Health
فهرسة مساهمة: Keywords: Cpi-17 (ppp1r14a); Danio rerio; Mypt1; PP1; Phi-1 (ppp1r14b); genome duplication
المشرفين على المادة: 0 (Fish Proteins)
0 (Intracellular Signaling Peptides and Proteins)
0 (Muscle Proteins)
0 (Proteins)
0 (phosphoprotein phosphatase inhibitor 1)
EC 3.1.3.16 (Phosphoprotein Phosphatases)
تواريخ الأحداث: Date Created: 20200814 Date Completed: 20210222 Latest Revision: 20210222
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7460850
DOI: 10.3390/ijms21165709
PMID: 32784920
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms21165709