Src Homology Domain 2-containing Tyrosine Phosphatase 2 Associates with Intercellular Adhesion Molecule 1 to Regulate Cell Survival

• Published in: The Journal of biological chemistry 2000-09, Vol.275 (39), p.30029-30036
• Main Authors: Pluskota, Elzbieta, Chen, Yiming, D'Souza, Stanley E.
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Cell Survival - physiology; Cells, Cultured; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Fibrinogen - metabolism; Intercellular Adhesion Molecule-1 - metabolism; Intracellular Signaling Peptides and Proteins; Peptide Fragments - metabolism; Phosphopeptides - metabolism; Phosphoproteins - metabolism; Phosphorylation; Protein Binding; Protein Phosphatase 2; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases - metabolism; Receptors, Immunologic - antagonists & inhibitors; SH2 Domain-Containing Protein Tyrosine Phosphatases; src Homology Domains; Tumor Necrosis Factor-alpha - pharmacology; Tyrosine - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M000240200

Intercellular adhesion molecule-1 (ICAM-1) binds to the plasma protein fibrinogen (Fg) to mediate leukocyte/endothelial cell interactions. In our studies, the ligation of Fg to ICAM-1 on tumor necrosis factor-α-stimulated endothelial cells resulted in the tyrosine phosphorylation of Src homology domain 2 (SH2)-containing phosphatase-2 (SHP-2). The ICAM-1 cytoplasmic sequence IKKYRLQ conforms poorly to the concensus immunoreceptor tyrosine-based inhibition motifs found in receptors that bind SHP-2. Nevertheless, the tyrosine phosphorylated sequence (IKKpYRLQ) bound specifically to the SH2 domain proximal to the NH2-terminal of SHP-2 (SHP-2-N) but not to the SH2 domain proximal on the COOH-terminal side (SHP-2-C). Phosphorylated ICAM-1 bound SHP-2-N. In immunoprecipitation experiments, SHP-2 associated with phosphorylated ICAM-1. Cells expressing truncated ICAM-1 that lacked the cytoplasmic sequence (ICAM-1(TR)) failed to associate with SHP-2. ICAM-1 containing the tyrosine to alanine substitution at position 485 (ICAM-1(Y485A)) associated weakly with SHP-2. Cells expressing ICAM-1(TR) and ICAM-1(Y485A) underwent apoptosis upon adhesion to Fg, whereas the wild type ICAM-1 maintained cell survival. These results indicate that ICAM-1 interactions with SHP-2 allow better cellular survival mediated through Fg-ICAM-1 ligation.