Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase

1990 ◽  
Vol 10 (5) ◽  
pp. 1853-1862
Author(s):  
A S Shaw ◽  
J Chalupny ◽  
J A Whitney ◽  
C Hammond ◽  
K E Amrein ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Metal Ion ◽  
Cytoplasmic Domain ◽  
Sequence Motif ◽  
Cytoplasmic Domains ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Tyrosine Protein Kinase ◽  
Amino Terminal Domain

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.

scholarly journals Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase.

1990 ◽  
Vol 10 (5) ◽  
pp. 1853-1862 ◽  
Author(s):  
A S Shaw ◽  
J Chalupny ◽  
J A Whitney ◽  
C Hammond ◽  
K E Amrein ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Metal Ion ◽  
Cytoplasmic Domain ◽  
Sequence Motif ◽  
Cytoplasmic Domains ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Tyrosine Protein Kinase ◽  
Amino Terminal Domain

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.

The Ick tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain

Cell ◽  
1989 ◽  
Vol 59 (4) ◽  
pp. 627-636 ◽  
Author(s):  
Andrey S. Shaw ◽  
Kurt E. Amrein ◽  
Craig Hammond ◽  
David F. Stern ◽  
Bartholomew M. Sefton ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cytoplasmic Tail ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Tyrosine Protein Kinase ◽  
Amino Terminal Domain

p59fyn tyrosine kinase associates with multiple T-cell receptor subunits through its unique amino-terminal domain

1992 ◽  
Vol 12 (12) ◽  
pp. 5438-5446
Author(s):  
L K Timson Gauen ◽  
A N Kong ◽  
L E Samelson ◽  
A S Shaw
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Mutational Analysis ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Amino Terminal Domain

Several lines of evidence link the protein tyrosine kinase p59fyn to the T-cell receptor. The molecular basis of this interaction has not been established. Here we show that the tyrosine kinase p59fyn can associate with chimeric proteins that contain the cytoplasmic domains of CD3 epsilon, gamma, zeta (zeta), and eta. Mutational analysis of the zeta cytoplasmic domain demonstrated that the membrane-proximal 41 residues of zeta are sufficient for p59fyn binding and that at least two p59fyn binding domains are present. The association of p59fyn with the zeta chain was specific, as two closely related Src family protein tyrosine kinases, p60src and p56lck, did not associate with a chimeric protein that contained the cytoplasmic domain of zeta. Mutational analysis of p59fyn revealed that a 10-amino-acid sequence in the unique amino-terminal domain of p59fyn was responsible for the association with zeta. These findings support evidence that p59fyn is functionally and structurally linked to the T-cell receptor. More importantly, these studies support a critical role for the unique amino-terminal domains of Src family kinases in the coupling of tyrosine kinases to the signalling pathways of cell surface receptors.

scholarly journals Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein Gp210.

1993 ◽  
Vol 178 (6) ◽  
pp. 2237-2242 ◽  
Author(s):  
R E Nickowitz ◽  
H J Worman
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Primary Biliary Cirrhosis ◽  
Antigenic Determinants ◽  
Nuclear Pore ◽  
Biliary Cirrhosis ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Carboxy Terminal ◽  
Amino Terminal Domain

Patients with primary biliary cirrhosis (PBC) frequently have autoantibodies against a 210-kD integral glycoprotein of the nuclear envelope pore membrane. This protein, termed gp210, has a 1,783-amino acid amino-terminal domain located in the perinuclear space, a 20-amino acid transmembrane segment, and a 58-amino acid cytoplasmic carboxy-terminal tail. We now demonstrate that autoantibodies from 25 patients with PBC that recognize gp210 react with the cytoplasmic carboxy-terminal tail while none react with unmodified linear epitopes in the amino-terminal domain. The epitope(s) recognized by autoantibodies from all 25 patients is contained within a stretch of 15 amino acids. The recognized amino acid sequence is homologous to the protein products of the Escherichia coli mutY gene and Salmonella typhimurium mutB gene with an exact identity of six consecutive amino acids, suggesting that anti-gp210 antibodies may arise by molecular mimicry of bacterial antigenic determinants.

Human Topoisomerase I is Phosphorylafedin vitroon its Amino Terminal Domain by Protein Kinase NII

1994 ◽  
Vol 375 (4) ◽  
pp. 255-260 ◽  
Author(s):  
Elena Cardellini ◽  
Massimo Bramucci ◽  
Gian Luigi Gianfranceschi ◽  
Egon Durban
Keyword(s):  
Protein Kinase ◽  
Topoisomerase I ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Amino Terminal Domain

scholarly journals p59fyn tyrosine kinase associates with multiple T-cell receptor subunits through its unique amino-terminal domain.

1992 ◽  
Vol 12 (12) ◽  
pp. 5438-5446 ◽  
Author(s):  
L K Timson Gauen ◽  
A N Kong ◽  
L E Samelson ◽  
A S Shaw
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
T Cell Receptor ◽  
Tyrosine Kinases ◽  
Mutational Analysis ◽  
Cell Receptor ◽  
Cytoplasmic Domain ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Amino Terminal Domain

Several lines of evidence link the protein tyrosine kinase p59fyn to the T-cell receptor. The molecular basis of this interaction has not been established. Here we show that the tyrosine kinase p59fyn can associate with chimeric proteins that contain the cytoplasmic domains of CD3 epsilon, gamma, zeta (zeta), and eta. Mutational analysis of the zeta cytoplasmic domain demonstrated that the membrane-proximal 41 residues of zeta are sufficient for p59fyn binding and that at least two p59fyn binding domains are present. The association of p59fyn with the zeta chain was specific, as two closely related Src family protein tyrosine kinases, p60src and p56lck, did not associate with a chimeric protein that contained the cytoplasmic domain of zeta. Mutational analysis of p59fyn revealed that a 10-amino-acid sequence in the unique amino-terminal domain of p59fyn was responsible for the association with zeta. These findings support evidence that p59fyn is functionally and structurally linked to the T-cell receptor. More importantly, these studies support a critical role for the unique amino-terminal domains of Src family kinases in the coupling of tyrosine kinases to the signalling pathways of cell surface receptors.

Assembly properties of altered beta-tubulin polypeptides containing disrupted autoregulatory domains

1989 ◽  
Vol 9 (8) ◽  
pp. 3418-3428
Author(s):  
W Gu ◽  
N J Cowan
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Beta Tubulin ◽  
Alpha Tubulin ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Tubulin Isotype ◽  
The Stability ◽  
Carboxy Terminal ◽  
Amino Terminal Domain

beta-Tubulin synthesis in eucaryotic cells is subject to control by an autoregulatory posttranscriptional mechanism in which the first four amino acids of the beta-tubulin polypeptide act either directly or indirectly to control the stability of beta-tubulin mRNA. To investigate the contribution of this amino-terminal domain to microtubule assembly and dynamics, we introduced a series of deletions encompassing amino acids 2 to 5 of a single mammalian beta-tubulin isotype, M beta 1. Constructs carrying such deletions were inserted into an expression vector, and the ability of the altered polypeptide to coassemble into microtubules was tested by using an anti-M beta 1-specific antibody. We show that the M beta 1 beta-tubulin polypeptide was competent for coassembly into microtubules in transient transfection experiments and in stably transfected cell lines when it lacked either amino acid 2 or amino acids 2 and 3. The capacity of these mutant beta-tubulins to coassemble into polymerized microtubules was only slightly diminished relative to that of unaltered beta-tubulin, and their expression did not influence the viability or growth properties of cell lines carrying these deletions. However, more extensive amino-terminal deletions either severely compromised or abolished the capacity for coassembly. In analogous experiments in which alterations were introduced into the amino-terminal domain of a mammalian alpha-tubulin isotype, M alpha 4, deletion of amino acid 2 did not affect the ability of the altered polypeptide to coassemble, although removal of additional amino-terminal residues essentially abolished the capacity for competent coassembly. The stability of the altered assembly-competent alpha- and beta-tubulin polypeptides was measured in pulse-chase experiments and found to be indistinguishable from the stability of the corresponding unaltered polypeptides. An assembly-competent M alpha 4 polypeptide carrying a deletion encompassing the 12 carboxy-terminal amino acids also had a half-life indistinguishable from that of the wild-type alpha-tubulin molecule. These data suggest that the universally conserved amino terminus of beta-tubulin acts largely in a regulatory role and that the carboxy-terminal domain of alpha-tubulin is not essential for coassembly in mammalian cells in vivo.

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