Involvement of p72syk kinase, p53/56lyn kinase and phosphatidyl inositol-3 kinase in signal transduction via the human B lymphocyte antigen CD22.
CD22 is a B lymphocyte-specific membrane protein that functions as an adhesion molecule via its interactions with a subset of alpha 2-6-linked sialic acid-containing glycoproteins. Engagement of CD22 with a monoclonal antibody (HB22.23) that blocks the binding of CD22 to its ligands results in rapid CD22 tyrosine phosphorylation and in increased association of CD22 with p53/56lyn kinase, p85 phosphatidyl inositol-3 kinase, and p72syk kinase. Synthetic peptides that span various regions of the intracellular portion of CD22 were used to map potential kinase binding sites. All three kinases associated with a tyrosine-phosphorylated peptide that spans tyrosine amino acid residues 822 and 842, implicating this as an important region in mediating CD22 signal transduction. In addition, purified p56lyn directly bound to the same peptide. Engagement of CD22 with HB22.23 was sufficient to stimulate normal B cell proliferation. This study further substantiates the importance of CD22 as a B lymphocyte signaling molecule and begins to unravel the mechanisms by which CD22 cross-linking can alter B cell function.
Tuscano
J M
JM
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA.
Engel
P
P
Tedder
T F
TF
Agarwal
A
A
Kehrl
J H
JH
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules; D017931:DNA Primers / Q000737:chemistry; D004792:Enzyme Precursors / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011940:Receptor Aggregation; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000502:physiology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D046911:Macromolecular Substances; D051918:Sialic Acid Binding Ig-like Lectin 2; D019000:Phosphotyrosine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases