The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis

Bukczynska, P., Klingler-Hoffmann, M., Mitchelhill, K. I., Lam, M. H. C., Ciccomancini, M., Tonks, N. K., Sarcevic, B., Kemp, B. E., Tiganis, T. (June 2004) The T-cell protein tyrosine phosphatase is phosphorylated on Ser-304 by cyclin-dependent protein kinases in mitosis. Biochemical Journal, 380. pp. 939-949. ISSN 0264-6021

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URL: https://www.ncbi.nlm.nih.gov/pubmed/15030318
DOI: 10.1042/BJ20031780

Abstract

Two alternatively spliced forms of the human protein tyrosine phosphatase TCPTP (T-cell protein tyrosine phosphatase) exist: a 48 kDa form that is targeted to the endoplasmic reticulum (TC48) and a shorter 45 kDa form that is targeted to the nucleus (TC45). In this study we have identified Ser-304 (Phe(301)-Asp-His-Ser(304)-Pro-Asn-Lys(307)) as a major TCPTP phosphorylation site and demonstrate that TC45, but not TC48, is phosphorylated on this site in vivo. Phosphorylation of TC45 on Ser-304 was cell cycle-dependent, and increased as cells progressed from G(2) into mitosis, but subsided upon mitotic exit. Ser304 phosphorylation was increased when cells were arrested in mitosis by microtubule poisons such as nocodazole, but remained unaltered when cells were arrested at the G(2)/M checkpoint by adriamycin. Phosphorylation of Ser-304 did not alter significantly the phosphatase activity or the protein stability of TC45, and had no apparent effect on TC45 localization. Ser-304 phosphorylation was ablated when cells were treated with the CDK (cyclindependent protein kinase) inhibitors roscovitine or SU9516, but remained unaltered when ERK1/2 activation was inhibited with the MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase) inhibitor PD98059. In addition, recombinant CDKs, but not the Polo-like kinase Plk1, phosphorylated Ser-304 in vitro. Our studies identify Ser-304 as a major phosphorylation site in human TCPTP, and the TC45 variant as a novel mitotic CDK substrate.

Item Type: Paper
Uncontrolled Keywords: alternative splicing and phosphorylation cell cycle cyclin-dependent protein kinase (CDK) CDK mitosis protein tyrosine phosphatase TC45 GROWTH-FACTOR RECEPTOR growth factor receptor G(2)/M TRANSITION transition REGULATORY SITES regulatory sites ACTIVATION activation TCPTP IDENTIFICATION identification EXPRESSION expression CHECKPOINTS checkpoints FIBROBLASTS fibroblasts INHIBITOR inhibitor
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:
Communities: CSHL labs > Tonks lab
Depositing User: CSHL Librarian
Date: June 2004
Date Deposited: 14 Feb 2012 17:10
Last Modified: 21 Feb 2017 20:59
PMCID: PMC1224230
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22334

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