Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase.
We report that the cytoplasmic domains of the T-lymphocyte glycoproteins CD4 and CD8 alpha contain short related amino acid sequences that are involved in binding the amino-terminal domain of the intracellular tyrosine protein kinase, p56lck. Transfer of as few as six amino acid residues from the cytoplasmic domain of the CD8 alpha protein to the cytoplasmic domain of an unrelated protein conferred p56lck binding to the hybrid protein in HeLa cells. The common sequence motif shared by CD4 and CD8 alpha contains two cysteines, and mutation of either cysteine in the CD4 sequence eliminated binding of p56lck.p56lck also contains two cysteine residues within its CD4-CD8 alpha-binding domain, and both are critical to the interaction with CD4 or CD8 alpha. Because the interaction does not involve disulfide bond formation, a metal ion could stabilize the complex.
Shaw
A S
AS
Department of Pathology, Yale School of Medicine, Yale University, New Haven, Connecticut 06510.
Chalupny
J
J
Whitney
J A
JA
Hammond
C
C
Amrein
K E
KE
Kavathas
P
P
Sefton
B M
BM
Rose
J K
JK
D000595:Amino Acid Sequence; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens; D003545:Cysteine / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004252:DNA Mutational Analysis; D006801:Humans; D066298:In Vitro Techniques; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D003545:Cysteine