Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex.
B cell antigen receptors are multicomponent complexes consisting of the surface immunoglobulin and accessory molecules with associating protein-tyrosine kinases. A spleen tyrosine kinase, Syk, in porcine B cells and a 72-kDa protein-tyrosine kinase, PTK72, in murine B cells associate with the B cell antigen receptor. Herein, we report the isolation of a full-length cDNA encoding the human homologue of Syk. This cDNA predicted a polypeptide consisting of two NH2-terminal SH2 domains and a COOH-terminal tyrosine kinase domain. Syk is highly conserved between human and swine and is homologous to the T cell-associated protein-tyrosine kinase ZAP-70. Both Syk mRNA and protein were detected in cells derived from multiple hematopoietic lineages. Within the B cell compartment, Syk was expressed from pro-B cells to plasma cells. In vitro kinase assays conducted on the human Syk protein isolated from B cells revealed the presence of autophosphorylation activity on Syk tyrosine residues. Tyrosine phosphorylation of Syk associating with the B cell receptor complex in human was augmented rapidly after surface immunoglobulin cross-linking. The human SYK locus was mapped to chromosome 9 at band q22.
Law
C L
CL
Department of Microbiology, University of Washington, Seattle 98195.
Sidorenko
S P
SP
Chandran
K A
KA
Draves
K E
KE
Chan
A C
AC
Weiss
A
A
Edelhoff
S
S
Disteche
C M
CM
Clark
E A
EA
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular / Q000379:methods; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000032:analysis; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000302:isolation & purification* / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000201:enzymology; D013552:Swine; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D018076:DNA, Complementary; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse