Association of phosphatidylinositol 3‐kinase with the photo‐oncogene product Cbl upon CD38 ligation by a specific monoclonal antibody in THP‐1 cells

Abstract

We reported that ecto-NAD + glycohydrolase activity induced upon differentiation of HL-60 cells with retinoic acid is localized on the extracellular domain of CD38 and that CD38 ligation by a specific monoclonal antibody, HB-7, is followed by rapid tyrosine phosphorylation of cellular proteins including a proto-oncogene product, Cbl. In the present study, we investigated intraceHular signaling linked to the HB-7-induced Cbl phosphorylation in dibutyryl cAMP-treated THP-1 cells. The 85-kDa regulatory subonit (p85) of phosphatidylinositul (PI) 3-kinase was immunoprecipitated with anti-Cbl antibody in a manner dependent on the tyrosine phosphorylation of Cbl. PI 3-kinase activity was also observed in the immunoprecipitated fractions containing tyrosine-phosphorylated Cbl. The phosphorylated form of Cbl, which had been separated from the CD38-stimulated cells, was capable of directly binding to a recombinant p85 fused to glutathione S-transferase. Thus, the direct association of tyrosine-phosphorylated Cbl with PI 3-kinase, possibly leading to the kinase activation, appeared to be involved in intracellular signaling caused by the CD38 ligation.

CD38 expressed on human monocytes: A coaccessory molecule in the superantigen-induced proliferation

“…This result is in agreement with independent studies demonstrating that c-Cbl is tyrosine phosphorylated after CD38 engagement in T cells (29), B cells (40), and myeloid cells (31,32). Among the many others proteins that display increased tyrosine phosphorylation in activated monocytes, we next focused our attention on the substrates activated via either CD38 or MHC Class II.…”

“…The candidate coreceptor we took into consideration was CD38, a surface molecule with pleiotropic functions (12,31,32,(36)(37)(38)(39)(40)(41).…”

D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites

“…c-Cbl has been shown to directly associate with the EGF receptor, and is phosphorylated in an EGF receptor dependent manner (Bowtell and Langdon, 1995;Fukazawa et al, 1995;Galisteo et al, 1995;Meisner et al, 1995;Odai et al, 1995;Solto and Cantley, 1996;Tanaka et al, 1995). c-Cbl has recently been linked to signalling by several di erent cytokine receptors including the Fcg receptor (Matsuo et al, 1996), B-cell receptor (Cory et al, 1995;Panchamoorthy et al, 1996), T-cell receptor (Donovan et al, 1994(Donovan et al, , 1996Lupher et al, 1996;Reedquist et al, 1996), and c-Kit receptor (Wisniewski et al, 1996). c-Cbl also associates with a range of intracellular proteins, including the p85 subunit of phosphatidylinositol 3'-kinase (Hartley and Corvera, 1996;Meisner et al, 1995), Crk Ribon et al, 1996;Sattler et al, 1996), Nck (Riverolezcano et al, 1994), CrkL (Andoniou et al, 1996;Sattler et al, 1996), SHC , cytoplasmic tyrosine kinases (Lupher et al, 1996;Panchamoorthy et al, 1996) and Grb2 (Buday et al, 1996;Donovan et al, 1996;Meisner et al, 1995;Odai et al, 1995).…”

Beyond the RING: CBL proteins as multivalent adapters

“…Consistent with these results, c-Cbl protein has been found in cells of lymphoid lineage, including multiple T-cell lines (Blake and Langdon, 1992;Cory et al, 1995;Donovan et al, 1994;Hartley et al, 1995;Mushinski et al, 1994), primary T cells (Marengere et al, 1997;Salojin et al, 1997), numerous lines of Bcellular origin (Cory et al, 1995;Hartley et al, 1995;Okuda et al, 1996;Panchamoorthy et al, 1996;Smit et al, 1996b;Uddin et al, 1996), primary B cells (Kim et al, 1995;Nishizumi et al, 1995), and NK cells (Cerboni et al, 1998;Gesbert et al, 1998). c-Cbl protein has also been found in various cells of myeloid lineage, including multiple myeloid progenitor cell lines (de Jong et al, 1995;Kanagasundaram et al, 1996;Marcilla et al, 1995;Oda et al, 1996;Odai et al, 1995;Okuda et al, 1996;Rivero-Lezcano et al, 1994;Wisniewski et al, 1996), monocytic cell lines and primary macrophages (Erdreich-Epstein et al, 1997; Kanagasundaram et al, 1996;Matsuo et al, 1996b;Tanaka et al, 1995), primary neutrophils (Brizzi et al, 1998;Naccache et al, 1997), eosinophils (Kato et al, 1998), mast cells Suzuki et al, 1997), a megakaryoblastic cell line (Brizzi et al, 1996;Sasaki et al, 1995) and platelets (Oda et al, 1996). c-Cbl protein is also present in osteoclasts and osteoblasts …”

“…Furthermore, c-Cbl becomes tyrosine phosphorylated in response to ligation of multiple cell surface receptors, such as Fas (Schlottmann et al, 1996) and CD2 (Lin et al, 2001;Umehara et al, 1998) in Jurkat T-cell line, CD5 in thymocytes (Dennehy et al, 1998), CD19 in A20 and DT40 B-cell lines (Beitz et al, 1999), CD28 in primary and Jurkat T cells (Slavik et al, 1999), CD38 in immature B cells Kitanaka et al, 1996), dierentiated myelomonocytic cell lines (Kontani et al, 1996;Matsuo et al, 1996b) and primary NK cells (Mallone et al, 2001), CD43 in MO7e megakaryoblastic cells (Anzai et al, 1999), and CD46 in primary T cells (Astier et al, 2000).…”