The SH2 domain containing tyrosine phosphatase-1 down-regulates activation of Lyn and Lyn-induced tyrosine phosphorylation of the CD19 receptor in B cells

Ally-Khan Somani, Kenneth Yuen, Fenhao Xu, Jinyi Zhang, Donald R. Branch, Katherine A. Siminovitch

Research output: Contribution to journalArticle

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Abstract

SHP-1 is a cytosolic tyrosine phosphatase implicated in down-regulation of B cell antigen receptor signaling. SHP-1 effects on the antigen receptor reflect its capacity to dephosphorylate this receptor as well as several inhibitory comodulators. In view of our observation that antigen receptor-induced CD19 tyrosine phosphorylation is constitutively increased in B cells from SHP-1-deficient motheaten mice, we investigated the possibility that CD19, a positive modulator of antigen receptor signaling, represents another substrate for SHP-1. However, analysis of CD19 coimmunoprecipitable tyrosine phosphatase activity in CD19 immunoprecipitates from SHP-1-deficient and wild-type B cells revealed that SHP-1 accounts for only a minor portion of CD19-associated tyrosine phosphatase activity. As CD19 tyrosine phosphorylation is modulated by the Lyn protein-tyrosine kinase, Lyn activity was evaluated in wild-type and motheaten B cells. The results revealed both Lyn as well as CD19-associated Lyn kinase activity to be constitutively and inducibly increased in SHP-1-deficient compared with wild-type B cells. The data also demonstrated SHP-1 to be associated with Lyn in stimulated but not in resting B cells and indicated this interaction to be mediated via Lyn binding to the SHP-1 N-terminal SH2 domain. These findings, together with cyanogen bromide cleavage data revealing that SHP-1 dephosphorylates the Lyn autophosphorylation site, identify Lyn deactivation/dephosphorylation as a likely mechanism whereby SHP-1 exerts its influence on CD19 tyrosine phosphorylation and, by extension, its inhibitory effect on B cell antigen receptor signaling.

Original languageEnglish (US)
Pages (from-to)1938-1944
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number3
StatePublished - Jan 19 2001
Externally publishedYes

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Phosphorylation
src Homology Domains
Phosphoric Monoester Hydrolases
Tyrosine
B-Lymphocytes
Down-Regulation
Chemical activation
Cells
Antigen Receptors
B-Cell Antigen Receptors
Cyanogen Bromide
Cell Communication
Modulators
Phosphotransferases
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

The SH2 domain containing tyrosine phosphatase-1 down-regulates activation of Lyn and Lyn-induced tyrosine phosphorylation of the CD19 receptor in B cells. / Somani, Ally-Khan; Yuen, Kenneth; Xu, Fenhao; Zhang, Jinyi; Branch, Donald R.; Siminovitch, Katherine A.

In: Journal of Biological Chemistry, Vol. 276, No. 3, 19.01.2001, p. 1938-1944.

Research output: Contribution to journalArticle

Somani, Ally-Khan ; Yuen, Kenneth ; Xu, Fenhao ; Zhang, Jinyi ; Branch, Donald R. ; Siminovitch, Katherine A. / The SH2 domain containing tyrosine phosphatase-1 down-regulates activation of Lyn and Lyn-induced tyrosine phosphorylation of the CD19 receptor in B cells. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 3. pp. 1938-1944.
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