CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling

Junko Irie-Sasaki, Takehiko Sasaki (), Wataru Matsumoto, Anne Opavsky, Mary Cheng, Grant Welstead, Emily Griffiths, Connie Krawczyk, Christopher D. Richardson, Karen Aitken, Norman Iscove, Gary Koretzky, Pauline Johnson, Peter Liu, David M. Rothstein and Josef M. Penninger
Additional contact information
Junko Irie-Sasaki: Amgen Institute, Ontario Cancer Institute, University of Toronto
Takehiko Sasaki: Amgen Institute, Ontario Cancer Institute, University of Toronto
Wataru Matsumoto: Department of Internal Medicine Yale University School of Medicine
Anne Opavsky: Heart and Stroke/Lewar Centre of Excellence in Cariovascular Research, University Health Network, University of Toronto
Mary Cheng: Amgen Institute, Ontario Cancer Institute, University of Toronto
Grant Welstead: Amgen Institute, Ontario Cancer Institute, University of Toronto
Emily Griffiths: Amgen Institute, Ontario Cancer Institute, University of Toronto
Connie Krawczyk: Amgen Institute, Ontario Cancer Institute, University of Toronto
Christopher D. Richardson: Amgen Institute, Ontario Cancer Institute, University of Toronto
Karen Aitken: Heart and Stroke/Lewar Centre of Excellence in Cariovascular Research, University Health Network, University of Toronto
Norman Iscove: Ontario Cancer Institute
Gary Koretzky: University of Pennsylvania School of Medicine
Pauline Johnson: Departments of Microbiology and Immunology University of British Columbia
Peter Liu: Heart and Stroke/Lewar Centre of Excellence in Cariovascular Research, University Health Network, University of Toronto
David M. Rothstein: Department of Internal Medicine Yale University School of Medicine
Josef M. Penninger: Amgen Institute, Ontario Cancer Institute, University of Toronto

Nature, 2001, vol. 409, issue 6818, 349-354

Abstract: Abstract The regulation of tyrosine phosphorylation and associated signalling through antigen, growth-factor and cytokine receptors is mediated by the reciprocal activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases)1. The transmembrane PTPase CD45 is a key regulator of antigen receptor signalling in T and B cells2,3. Src-family kinases have been identified as primary molecular targets for CD45 (ref. 4). However, CD45 is highly expressed in all haematopoietic lineages at all stages of development5, indicating that CD45 could regulate other cell types and might act on additional substrates. Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. Targeted disruption of the cd45 gene leads to enhanced cytokine and interferon-receptor-mediated activation of JAKs and STAT (signal transducer and activators of transcription) proteins. In vitro , CD45 directly dephosphorylates and binds to JAKs. Functionally, CD45 negatively regulates interleukin-3-mediated cellular proliferation, erythropoietin-dependent haematopoieisis and antiviral responses in vitro and in vivo. Our data identify an unexpected and novel function for CD45 as a haematopoietic JAK phosphatase that negatively regulates cytokine receptor signalling.

Date: 2001
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/35053086 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:409:y:2001:i:6818:d:10.1038_35053086

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35053086

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().