T. Matozaki et al., MOLECULAR-CLONING OF A HUMAN TRANSMEMBRANE-TYPE PROTEIN-TYROSINE-PHOSPHATASE AND ITS EXPRESSION IN GASTROINTESTINAL CANCERS, The Journal of biological chemistry, 269(3), 1994, pp. 2075-2081
To determine the expression of various protein-tyrosine phosphatases (
PTPs) in human gastric cancers, cDNAs encoding conserved PTP domains w
ere amplified by reverse transcriptase polymerase chain reaction from
KATO-III cell mRNA and sequenced. Among 72 polymerase chain reaction c
lones, one of the cDNA sequences encoded a novel potential PTP (stomac
h cancer-associated PTP, SAP-I). The full length (3.9 kilo-bases) of t
he SAP-I cDNA was further isolated from the KATO-III cell cDNA library
and the WiDr cell cDNA library. The predicted amino acid sequence of
the SAP-1 cDNA showed that mature SAP-1 consisted of 1093 amino acids
and a transmembrane-type PTP, which possessed a single PTP-conserved d
omain in the cytoplasmic region. The extracellular region of SAP-1 con
sisted of eight fibronectin type III-like structure repeats and contai
ned multiple N-glycosylation sites. These data suggest that SAP-1 is s
tructurally similar to HPTPbeta and that SAP-1 and HPTPbeta represent
a subfamily of transmembrane-type PTPs. SAP-1 was mainly expressed in
brain and liver and at a lower level in heart and stomach as a 4.2-kil
obase mRNA, but it was not detected in pancreas or colon. In contrast,
among cancer cell lines tested, SAP-1 was highly expressed in pancrea
tic and colorectal cancer cells. The bacterially expressed SAP-1 fusio
n protein had tyrosine-specific phosphatase activity. Immunoblotting w
ith anti-SAP-1 antibody showed that SAP-1 is a 200-kDa protein. In add
ition, transient transfection of SAP-1 cDNA to COS cells resulted in t
he predominant expression of a 200-kDa protein recognized by anti-SAP-
1 antibody. SAP-1 is mapped to chromosome 19 region q13.4 and might be
related to carcinoembryonic antigen mapped to 19q13.2.