Isolation of a src homology 2-containing tyrosine phosphatase.
Tyrosine phosphorylation is controlled by the opposing actions of tyrosine kinases and phosphotyrosine phosphatases (PTPs). src homology 2 domains (SH2) are found in several types of signaling proteins, including some tyrosine kinases. These domains bind phosphotyrosyl proteins and thus help promote signal transduction. Using mixed oligonucleotide-directed polymerase chain reactions, two previously undescribed rat PTP cDNA fragments were generated. Through subsequent screening of rat megakaryocyte and human erythroleukemia libraries, we obtained a full-length coding sequence for one of these fragments. This cDNA, SH-PTP1, encodes a tyrosine phosphatase containing two highly conserved SH2 domains. SH-PTP1, with a 2.4-kilobase mRNA, a predicted open reading frame of 595 amino acids, and a structure suggesting a nontransmembrane protein, is expressed primarily in hematopoietic and epithelial cells. When expressed in Escherichia coli, SH-PTP1 possesses PTP activity. The structure of SH-PTP1 establishes an additional branch of the tyrosine phosphatase family and suggests mechanisms through which tyrosine phosphatases might participate in signal transduction pathways.
Plutzky
J
J
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02118.
Neel
B G
BG
Rosenberg
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D003001:Cloning, Molecular; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment
D012333:RNA, Messenger; D011994:Recombinant Proteins; D017027:Protein Tyrosine Phosphatases