PMID- 10864922 OWN - NLM STAT- MEDLINE DCOM- 20001027 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 275 IP - 39 DP - 2000 Sep 29 TI - Src homology domain 2-containing tyrosine phosphatase 2 associates with intercellular adhesion molecule 1 to regulate cell survival. PG - 30029-36 AB - 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-alpha-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 NH(2)-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. FAU - Pluskota, E AU - Pluskota E AD - Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. FAU - Chen, Y AU - Chen Y FAU - D'Souza, S E AU - D'Souza SE LA - eng GR - HL 43721/HL/NHLBI NIH HHS/United States GR - RR-00080/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Peptide Fragments) RN - 0 (Phosphopeptides) RN - 0 (Phosphoproteins) RN - 0 (Receptors, Immunologic) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 42HK56048U (Tyrosine) RN - 9001-32-5 (Fibrinogen) RN - EC 3.1.3.16 (Protein Phosphatase 2) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.48 (SH2 Domain-Containing Protein Tyrosine Phosphatases) SB - IM MH - Amino Acid Motifs MH - Cell Survival/*physiology MH - Cells, Cultured MH - Endothelium, Vascular/cytology/drug effects MH - Fibrinogen/metabolism MH - Intercellular Adhesion Molecule-1/*metabolism MH - Intracellular Signaling Peptides and Proteins MH - Peptide Fragments/metabolism MH - Phosphopeptides/metabolism MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Protein Binding MH - Protein Phosphatase 2 MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11 MH - Protein Tyrosine Phosphatase, Non-Receptor Type 6 MH - Protein Tyrosine Phosphatases/*metabolism MH - Receptors, Immunologic/antagonists & inhibitors MH - SH2 Domain-Containing Protein Tyrosine Phosphatases MH - Tumor Necrosis Factor-alpha/pharmacology MH - Tyrosine/metabolism MH - *src Homology Domains EDAT- 2000/06/24 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/06/24 11:00 PHST- 2000/06/24 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/06/24 11:00 [entrez] AID - S0021-9258(18)44330-X [pii] AID - 10.1074/jbc.M000240200 [doi] PST - ppublish SO - J Biol Chem. 2000 Sep 29;275(39):30029-36. doi: 10.1074/jbc.M000240200.