A new protein containing an SH2 domain that inhibits JAK kinases
- PMID: 9202126
- DOI: 10.1038/43213
A new protein containing an SH2 domain that inhibits JAK kinases
Abstract
The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signalling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine-phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway.
Similar articles
-
The JAK-inhibitor, JAB/SOCS-1 selectively inhibits cytokine-induced, but not v-Src induced JAK-STAT activation.Oncogene. 2000 Sep 28;19(41):4795-801. doi: 10.1038/sj.onc.1203829. Oncogene. 2000. PMID: 11032030
-
A family of cytokine-inducible inhibitors of signalling.Nature. 1997 Jun 26;387(6636):917-21. doi: 10.1038/43206. Nature. 1997. PMID: 9202125
-
Structure and function of a new STAT-induced STAT inhibitor.Nature. 1997 Jun 26;387(6636):924-9. doi: 10.1038/43219. Nature. 1997. PMID: 9202127
-
The CIS family: negative regulators of JAK-STAT signaling.Cytokine Growth Factor Rev. 1998 Sep-Dec;9(3-4):197-204. doi: 10.1016/s1359-6101(98)00019-7. Cytokine Growth Factor Rev. 1998. PMID: 9918119 Review.
-
Negative regulation of cytokine signaling pathways.Annu Rev Immunol. 2000;18:143-64. doi: 10.1146/annurev.immunol.18.1.143. Annu Rev Immunol. 2000. PMID: 10837055 Review.
Cited by
-
LIF signal in mouse embryonic stem cells.JAKSTAT. 2015 Sep 11;4(2):e1086520. doi: 10.1080/21623996.2015.1086520. eCollection 2015. JAKSTAT. 2015. PMID: 27127728 Free PMC article. Review.
-
Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity.Immunity. 2012 Feb 24;36(2):239-50. doi: 10.1016/j.immuni.2011.12.015. Immunity. 2012. PMID: 22342841 Free PMC article.
-
Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway.Br J Pharmacol. 2010 Oct;161(3):541-54. doi: 10.1111/j.1476-5381.2010.00874.x. Br J Pharmacol. 2010. PMID: 20880395 Free PMC article.
-
Suppressor of cytokine signaling-1 selectively inhibits LPS-induced IL-6 production by regulating JAK-STAT.Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17089-94. doi: 10.1073/pnas.0508517102. Epub 2005 Nov 15. Proc Natl Acad Sci U S A. 2005. PMID: 16287972 Free PMC article.
-
Cytokine-induced Src homology 2 protein (CIS) promotes T cell receptor-mediated proliferation and prolongs survival of activated T cells.J Exp Med. 2000 Mar 20;191(6):985-94. doi: 10.1084/jem.191.6.985. J Exp Med. 2000. PMID: 10727460 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
