Immunity. 2000 Jul;13(1):47-57.

CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification.

Fujimoto M, Fujimoto Y, Poe JC, Jansen PJ, Lowell CA, DeFranco AL, Tedder TF.

Source

Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

CD19 regulates constitutive and antigen receptor-induced signaling thresholds in B lymphocytes through its unique cytoplasmic domain. Herein, we demonstrate a novel molecular mechanism where interactions between CD19 and Lyn amplify basal and antigen receptor-induced Src family kinase activation. Lyn expression was required for CD19 tyrosine phosphorylation in primary B cells. Experiments with purified proteins demonstrated that CD19-Y513 was Lyn's initial phosphorylation and binding site. This led to processive phosphorylation of CD19-Y482, which recruited a second Lyn molecule, allowing for transphosphorylation and amplification of Lyn activation. In vivo, CD19 deficiency impaired, and CD19 overexpression enhanced, Lyn kinase activity. Thus, CD19 functions as a specialized adapter protein for the amplification of Src family kinases that is crucial for intrinsic and antigen receptor-induced signal transduction.

PMID:: 10933394; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

Research Support, U.S. Gov't, P.H.S.

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Molecular Biology Databases

Miscellaneous

Mouse Genome Informatics (MGI)

Supplemental Content

Related citations

CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation. [J Immunol. 1999]
CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation.
Fujimoto M, Poe JC, Jansen PJ, Sato S, Tedder TF. J Immunol. 1999 Jun 15; 162(12):7088-94.
A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice. [J Immunol. 2001]
A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice.
Hasegawa M, Fujimoto M, Poe JC, Steeber DA, Lowell CA, Tedder TF. J Immunol. 2001 Sep 1; 167(5):2469-78.
The activation and subsequent regulatory roles of Lyn and CD19 after B cell receptor ligation are independent. [J Immunol. 2002]
The activation and subsequent regulatory roles of Lyn and CD19 after B cell receptor ligation are independent.
Xu Y, Beavitt SJ, Harder KW, Hibbs ML, Tarlinton DM. J Immunol. 2002 Dec 15; 169(12):6910-8.
Review CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. [Immunol Res. 2000]
Review CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification.
Fujimoto M, Poe JC, Hasegawa M, Tedder TF. Immunol Res. 2000; 22(2-3):281-98.
Review Lyn tyrosine kinase: accentuating the positive and the negative. [Immunity. 2005]
Review Lyn tyrosine kinase: accentuating the positive and the negative.
Xu Y, Harder KW, Huntington ND, Hibbs ML, Tarlinton DM. Immunity. 2005 Jan; 22(1):9-18.

See reviews... See all...

Cited by 16 PubMed Central articles

CD133/Src axis mediates tumor initiating property and epithelial-mesenchymal transition of head and neck cancer. [PLoS One. 2011]
CD133/Src axis mediates tumor initiating property and epithelial-mesenchymal transition of head and neck cancer.
Chen YS, Wu MJ, Huang CY, Lin SC, Chuang TH, Yu CC, Lo JF. PLoS One. 2011; 6(11):e28053. Epub 2011 Nov 28.
The development of mature B lymphocytes requires the combined function of CD19 and the p110δ subunit of PI3K. [Self Nonself. 2010]
The development of mature B lymphocytes requires the combined function of CD19 and the p110δ subunit of PI3K.
Kövesdi D, Bell SE, Turner M. Self Nonself. 2010 Apr; 1(2):144-153. Epub 2010 Mar 11.
Review The conundrum of inhibitory signaling by ITAM-containing immunoreceptors: potential molecular mechanisms. [FEBS Lett. 2010]
Review The conundrum of inhibitory signaling by ITAM-containing immunoreceptors: potential molecular mechanisms.
Waterman PM, Cambier JC. FEBS Lett. 2010 Dec 15; 584(24):4878-82. Epub 2010 Sep 28.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
Gene (OMIM)
Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide
Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
OMIM (cited)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
Protein
Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes th...
CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification.
Immunity. 2000 Jul ;13(1):47-57.

PubMed
The F-actin cross-linking and focal adhesion protein filamin A is a ligand and i...
The F-actin cross-linking and focal adhesion protein filamin A is a ligand and in vivo substrate for protein kinase C alpha.
J Biol Chem. 2003 Jun 27 ;278(26):23561-9. Epub 2003 Apr 17 .

PubMed
BLNK mediates Syk-dependent Btk activation.
BLNK mediates Syk-dependent Btk activation.
Proc Natl Acad Sci U S A. 2001 Feb 27 ;98(5):2582-6. Epub 2001 Feb 13 .

PubMed
Internet-based cognitive rehabilitation in individuals with acquired brain injur...
Internet-based cognitive rehabilitation in individuals with acquired brain injury: a pilot feasibility study.
Brain Inj. 2008 Oct ;22(11):891-7.

PubMed
Phosphorylation of CD19 Y484 and Y515, and linked activation of phosphatidylinos...
Phosphorylation of CD19 Y484 and Y515, and linked activation of phosphatidylinositol 3-kinase, are required for B cell antigen receptor-mediated activation of Bruton's tyrosine kinase.
J Immunol. 1999 Apr 15 ;162(8):4438-46.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to: