PMID- 10092522 OWN - NLM STAT- MEDLINE DCOM- 19990511 LR - 20161124 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 257 IP - 1 DP - 1999 Apr 2 TI - The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase. PG - 129-38 AB - Hematopoietic cell kinase (Hck) is a member of the Src-family of protein tyrosine kinases. We have found that upon enzymatic activation of Hck by the heavy metal mercuric chloride, there was a rapid increase in the levels of tyrosine phosphorylation of several proteins including the proto-oncogene p120(Cbl). Fibroblasts that are transformed with an activated allele of Hck exhibit constitutive Cbl phosphorylation. Upon Fcgamma receptor activation, a more physiologically relevant extracellular signal, Cbl is tyrosine phosphorylated and the Src-family selective inhibitor, PP1, can prevent this phosphorylation on Cbl. Hck phosphorylates Cbl in vitro and the interaction between Cbl and Hck is direct, requiring Hck's unique, SH3 and SH2 domains for optimal binding. Using a novel estrogen-regulated chimera of Hck we have shown a hormone-dependent association between Hck and Cbl in murine fibroblasts. This work suggests that Cbl serves as a key mediator of Hck induced signalling in hematopoietic cells. CI - Copyright 1999 Academic Press. FAU - Howlett, C J AU - Howlett CJ AD - Department of Oncology, University of Calgary, Calgary, Alberta, Canada. FAU - Bisson, S A AU - Bisson SA FAU - Resek, M E AU - Resek ME FAU - Tigley, A W AU - Tigley AW FAU - Robbins, S M AU - Robbins SM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 0 (Receptors, IgG) RN - 0 (Recombinant Fusion Proteins) RN - 21820-51-9 (Phosphotyrosine) RN - 4TI98Z838E (Estradiol) RN - 53GH7MZT1R (Mercuric Chloride) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (HCK protein, human) RN - EC 2.7.10.2 (Hck protein, mouse) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck) RN - EC 6.3.2.- (CBL protein, human) RN - EC 6.3.2.- (Cbl protein, mouse) SB - IM MH - 3T3 Cells MH - Alleles MH - Animals MH - Cell Line, Transformed MH - Enzyme Activation/drug effects MH - Estradiol/pharmacology MH - Humans MH - Mercuric Chloride/pharmacology MH - Mice MH - Phosphorylation/drug effects MH - Phosphotyrosine/metabolism MH - Precipitin Tests MH - Protein Binding MH - Protein-Tyrosine Kinases/genetics/*metabolism MH - Proto-Oncogene Proteins/genetics/*metabolism MH - Proto-Oncogene Proteins c-cbl MH - Proto-Oncogene Proteins c-hck MH - Pyrazoles/pharmacology MH - Pyrimidines/pharmacology MH - Receptor Aggregation MH - Receptors, IgG/antagonists & inhibitors/metabolism MH - Recombinant Fusion Proteins/biosynthesis/metabolism MH - Transfection MH - Tumor Cells, Cultured MH - *Ubiquitin-Protein Ligases MH - src Homology Domains/physiology EDAT- 1999/03/27 00:00 MHDA- 1999/03/27 00:01 CRDT- 1999/03/27 00:00 PHST- 1999/03/27 00:00 [pubmed] PHST- 1999/03/27 00:01 [medline] PHST- 1999/03/27 00:00 [entrez] AID - S0006-291X(99)90427-8 [pii] AID - 10.1006/bbrc.1999.0427 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 1999 Apr 2;257(1):129-38. doi: 10.1006/bbrc.1999.0427.