Cloning of three human tyrosine phosphatases reveals a multigene family of receptor-linked protein-tyrosine-phosphatases expressed in brain.
A human brainstem cDNA library in bacteriophage lambda gt11 was screened under conditions of reduced hybridization stringency with a leukocyte common antigen (LCA) probe that spanned both conserved cytoplasmic domains. cDNA encoding a receptor-linked protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), RPTPase alpha, has been cloned and sequenced. Human RPTPase alpha consists of 802 amino acids. The extracellular domain of 150 residues includes a hydrophobic signal peptide and eight potential N-glycosylation sites. This is followed by a transmembrane region and two tandemly repeated conserved domains characteristic of all RPTPases identified thus far. The gene for RPTPase alpha has been localized to human chromosome region 20pter-20q12 by analysis of its segregation pattern in rodent-human somatic cell hybrids. Northern blot analysis revealed the presence of two major transcripts of 4.3 and 6.3 kilobases. In addition to RPTPase alpha, two other RPTPases (beta and gamma), identified in the same screen, have been partially cloned and sequenced. Analysis of sequence comparisons among LCA, the LCA-related protein LAR, and RPTPases alpha, beta, and gamma reveals the existence of a multigene family encoding different RPTPases, each containing a distinct extracellular domain, a single hydrophobic transmembrane region, and two tandemly repeated conserved cytoplasmic domains.
Kaplan
R
R
Rorer Biotechnology, Inc., King of Prussia, PA 19406.
Morse
B
B
Huebner
K
K
Croce
C
C
Howk
R
R
Ravera
M
M
Ricca
G
G
Jaye
M
M
Schlessinger
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002890:Chromosomes, Human, Pair 20; D003001:Cloning, Molecular; D015723:Gene Library; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D005810:Multigene Family; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases; D011956:Receptors, Cell Surface / Q000235:genetics*; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D011956:Receptors, Cell Surface; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases