Transmembrane homodimerization of receptor-like protein tyrosine phosphatases.
Receptor-like protein tyrosine phosphatases (RPTPs) are type I integral membrane proteins. Together with protein tyrosine kinases, RPTPs regulate the phosphotyrosine levels in the cell. Studies of two RPTPs, CD45 and PTPalpha, have provided strong evidence that dimerization leads to inactivation of the receptors, and that the dimerization of PTPalpha involves interactions in the transmembrane domain (TMD). Using the TOXCAT assay, a genetic approach for analyzing TM interactions in Escherichia coli membranes, we show that the TMD of RPTPs interact in the membrane, albeit to different extents. Using fusion proteins of TMDs, we also observe an equilibrium between monomer and dimer in sodium dodecyl sulfate (SDS) micelles. Through a mutational study of the DEP1 TMD, we demonstrate that these interactions are specific. Taken together, our results define a subset of the RPTP family in which TM homodimerization may act as a mediator of protein function.
Chin
Chen-Ni
CN
Department of Molecular Biophysics and Biochemistry, School of Medicine, Yale University, 266 Whitney Avenue, P.O. Box 208114, New Haven, CT 06520-8114, United States.
Sachs
Jonathan N
JN
Engelman
Donald M
DM
D000595:Amino Acid Sequence; D001681:Biological Assay; D002462:Cell Membrane / Q000378:metabolism; D004252:DNA Mutational Analysis; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008823:Micelles; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
D008823:Micelles; D011956:Receptors, Cell Surface; D012967:Sodium Dodecyl Sulfate; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3