B cell antigen receptor cross-linking induces phosphorylation of the p21ras oncoprotein activators SHC and mSOS1 as well as assembly of complexes containing SHC, GRB-2, mSOS1, and a 145-kDa tyrosine-phosphorylated protein - PubMed (original) (raw)

. 1994 Jul 15;153(2):623-36.

Affiliations

PMID: 8021500

B cell antigen receptor cross-linking induces phosphorylation of the p21ras oncoprotein activators SHC and mSOS1 as well as assembly of complexes containing SHC, GRB-2, mSOS1, and a 145-kDa tyrosine-phosphorylated protein

T M Saxton et al. J Immunol. 1994.

Abstract

Ligation of the B cell AgR activates p21ras (Ras). We have investigated the effects of AgR ligation on three proteins that have been implicated as regulators of Ras: SHC, GRB-2, and mSOS1. We show that AgR cross-linking in B cells stimulated tyrosine and serine phosphorylation of SHC. This correlated with the formation of complexes containing SHC, GRB-2, mSOS1, and an unidentified 145-kDa tyrosine-phosphorylated protein. These complexes were present in the cytosol, as well as in the membrane fraction of the cells, where Ras is located. By using a GRB-2 fusion protein to probe blots, we showed that SHC was the major protein that GRB-2 bound to in anti-Ig-stimulated B cells. This argues that SHC couples GRB-2/mSOS1 to the 145-kDa protein and that SHC is likely to be essential for mSOS1 function in B cells. Finally, we found that AgR cross-linking stimulated phosphorylation of mSOS1 and that this could be blocked by an inhibitor of protein kinase C. Thus, signaling by the B cell AgR stimulates phosphorylation of SHC and mSOS1 and induces the formation of membrane-associated complexes containing SHC, GRB-2, mSOS1, and a 145-kDa protein. These events may be important for activation of Ras by the AgR.

PubMed Disclaimer

Cited by

Altered antigen receptor signaling and impaired Fas-mediated apoptosis of B cells in Lyn-deficient mice.
Wang J, Koizumi T, Watanabe T. Wang J, et al. J Exp Med. 1996 Sep 1;184(3):831-8. doi: 10.1084/jem.184.3.831. J Exp Med. 1996. PMID: 9064343 Free PMC article.
Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer's disease.
Terzioglu G, Young-Pearse TL. Terzioglu G, et al. Mol Neurodegener. 2023 Nov 29;18(1):89. doi: 10.1186/s13024-023-00674-9. Mol Neurodegener. 2023. PMID: 38017562 Free PMC article. Review.
Regulation of RasGRP1 by B cell antigen receptor requires cooperativity between three domains controlling translocation to the plasma membrane.
Beaulieu N, Zahedi B, Goulding RE, Tazmini G, Anthony KV, Omeis SL, de Jong DR, Kay RJ. Beaulieu N, et al. Mol Biol Cell. 2007 Aug;18(8):3156-68. doi: 10.1091/mbc.e06-10-0932. Epub 2007 Jun 13. Mol Biol Cell. 2007. PMID: 17567957 Free PMC article.
Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptor-coupled tyrosine kinases.
Taniuchi I, Kitamura D, Maekawa Y, Fukuda T, Kishi H, Watanabe T. Taniuchi I, et al. EMBO J. 1995 Aug 1;14(15):3664-78. doi: 10.1002/j.1460-2075.1995.tb00036.x. EMBO J. 1995. PMID: 7641686 Free PMC article.
Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling.
Ravichandran KS, Igras V, Shoelson SE, Fesik SW, Burakoff SJ. Ravichandran KS, et al. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5275-80. doi: 10.1073/pnas.93.11.5275. Proc Natl Acad Sci U S A. 1996. PMID: 8643566 Free PMC article.

B cell antigen receptor cross-linking induces phosphorylation of the p21ras oncoprotein activators SHC and mSOS1 as well as assembly of complexes containing SHC, GRB-2, mSOS1, and a 145-kDa tyrosine-phosphorylated protein - PubMed (original) (raw)