PMID- 10415030
OWN - NLM
STAT- MEDLINE
DCOM- 19990812
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 3
DP  - 1999 Aug 1
TI  - CD45 negatively regulates lyn activity by dephosphorylating both positive and
      negative regulatory tyrosine residues in immature B cells.
PG  - 1321-6
AB  - Using CD45-deficient clones from the immature B cell line, WEHI-231, we
      previously demonstrated that CD45 selectively dephosphorylates the Src-family
      protein tyrosine kinase Lyn and inhibits its kinase activity. To further define
      the mechanisms of CD45 action on Lyn, we metabolically labeled Lyn from
      CD45-positive and -negative WEHI-231 cells and analyzed cyanogen bromide
      fragments by SDS-PAGE analysis. Phosphoamino acid analysis confirmed that Lyn is 
      tyrosine phosphorylated with little serine or threonine phosphorylation. In
      CD45-negative cells, two bands at 8.2 and 4.1 kDa were phosphorylated in the
      absence of B cell Ag receptor (BCR) ligation. The 8.2-kDa band corresponded to a 
      fragment containing the positive regulatory site (Tyr397), as assessed by its
      size and its phosphorylation in an in vitro kinase assay. The 4.1-kDa band was
      phosphorylated by COOH-terminal Src kinase, suggesting that it contains the
      COOH-terminal negative regulatory site (Tyr508). CD45 was also shown to
      dephosphorylate autophosphorylated Lyn in vitro. Thus, CD45 dephosphorylates not 
      only the negative but also the positive regulatory tyrosine residues of Lyn.
      Furthermore, coimmunoprecipitations using anti-Igalpha Ab demonstrated that Lyn
      associated with the resting BCR was constitutively phosphorylated and activated
      in CD45-negative cells. In the parental cells, both regulatory sites were
      phosphorylated on BCR ligation. Taken collectively, these results suggest that
      CD45 keeps both BCR-associated and total cytoplasmic pools of Lyn in an inactive 
      state, and a mechanism by which Lyn is activated by relative reduction of CD45
      effect may be operative on BCR ligation.
FAU - Katagiri, T
AU  - Katagiri T
AD  - Department of Microbiology and Immunology, Tokyo Metropolitan Institute for
      Neuroscience, Tokyo, Japan.
FAU - Ogimoto, M
AU  - Ogimoto M
FAU - Hasegawa, K
AU  - Hasegawa K
FAU - Arimura, Y
AU  - Arimura Y
FAU - Mitomo, K
AU  - Mitomo K
FAU - Okada, M
AU  - Okada M
FAU - Clark, M R
AU  - Clark MR
FAU - Mizuno, K
AU  - Mizuno K
FAU - Yakura, H
AU  - Yakura H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Macromolecular Substances)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.2 (lyn protein-tyrosine kinase)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - AIM
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/cytology/*enzymology/metabolism
MH  - Cell Differentiation/immunology
MH  - Clone Cells
MH  - Down-Regulation/genetics/*immunology
MH  - Enzyme Activation/genetics/immunology
MH  - Leukocyte Common Antigens/genetics/*physiology
MH  - Macromolecular Substances
MH  - Mice
MH  - Phosphorylation
MH  - Phosphotyrosine/*metabolism
MH  - Receptors, Antigen, B-Cell/metabolism
MH  - Tumor Cells, Cultured
MH  - src-Family Kinases/*antagonists & inhibitors/*metabolism
EDAT- 1999/07/22 00:00
MHDA- 1999/07/22 00:01
CRDT- 1999/07/22 00:00
PHST- 1999/07/22 00:00 [pubmed]
PHST- 1999/07/22 00:01 [medline]
PHST- 1999/07/22 00:00 [entrez]
AID - ji_v163n3p1321 [pii]
PST - ppublish
SO  - J Immunol. 1999 Aug 1;163(3):1321-6.