SHP-1 deficiency in B-lineage cells is associated with heightened lyn protein expression and increased lyn kinase activity.
SHP-1 protein tyrosine phosphatase is a critical regulator of signal transduction in hematopoietic cells. In the present study, we derived two pre-B cell lines, PBCL-1 and PBCL-2, from normal and SHP-1-deficient motheaten mice, respectively, and characterized hyperphosphorylated proteins in PBCL-2 cells to identify SHP-1-regulated molecules. Two proteins of 56 and 53 kDa (p56/p53) in PBCL-2 cells showed heightened phosphorylation (3- to 6-fold) in comparison with those in PBCL-1. p56/p53 were identified as the two forms of the lyn protein tyrosine kinase (p56/p53lyn), which showed increased kinase activity in PBCL-2 cells. Interestingly, the protein levels of p56/53lyn were found to be 3- to 6-fold higher in PBCL-2 cells than those in PBCL-1, whereas the transcript levels of lyn in the two cell lines were comparable. A modest increase in p56/53lyn protein expression was also detected in primary spleen B cells of motheaten mice. Thus SHP-1 deficiency in B-lineage cells, especially pre-B cells, is associated with increased lyn protein expression and kinase activity. These data indicate a role for SHP-1 in regulating lyn through a post-transcriptional mechanism.
Yang
W
W
Department of Cancer Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
Mckenna
S D
SD
Jiao
H
H
Tabrizi
M
M
Lynes
M A
MA
Shultz
L D
LD
Yi
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002478:Cells, Cultured; D015851:Interleukin-7 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency*; D013154:Spleen / Q000737:chemistry / Q000166:cytology; D014158:Transcription, Genetic; D019061:src-Family Kinases / Q000032:analysis / Q000378:metabolism*
D015851:Interleukin-7; D047908:Intracellular Signaling Peptides and Proteins; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse