The Janus kinase family and signaling through members of the cytokine receptor superfamily

Journal Article · Sat Dec 31 04:00:00 EST 1994 · Proceedings of the Society for Experimental Biology and Medicine

DOI:https://doi.org/10.3181/00379727-206-43757· OSTI ID:466623

Ihle, J N ^[1]

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1. St. Jude Children`s Research Hospital, Memphis, TN (United States)

Many cytokines initiate cellular responses through their interaction with members of the cytokine receptor superfamily which contain no catalytic domains in their cytoplasmic domains. Irrespective, ligand binding induces tyrosine phosphorylation, which requires a membrane proximal region of the cytoplasmic domain. Recent studies have shown that members of the Janus kinase (JAK) family of protein tyrosine kinases associate with the membrane proximal region, are rapidly tyrosine phosphorylated following ligand binding and their in vitro kinase activity is activated. The JAKs are 130-kDa proteins which lack SH2/SH3 domains and contain two kinase domains, an active domain and a second kinase-like domain. Individual receptors associate with, or require, one or more of the three known family members including JAK1, JAK2, and tyk2. Substrates of the JAKs include the 91-kDa and 113-kDa proteins of the interferon-stimulated transcription complex ISGF3. These proteins, when tyrosine phosphorylated, migrate to the nucleus and participate in the activation of gene transcription. Recent evidence suggests that the 91- and 113-kDa proteins are members of a large family of genes that are potential substrates of JAK family members and may regulate a variety of genes involved in cell growth, differentiation or function. 42 refs.

• Sponsoring Organization: USDOE
• OSTI ID: 466623
• Journal Information: Proceedings of the Society for Experimental Biology and Medicine, Journal Name: Proceedings of the Society for Experimental Biology and Medicine Vol. 206; ISSN PSEBAA; ISSN 0037-9727
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANIMAL CELLS
CELL DIFFERENTIATION
CELL MEMBRANES
CELL NUCLEI
GENE REGULATION
GENES
GROWTH
GROWTH FACTORS
INTERFERON
LIGANDS
LYMPHOKINES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRANSCRIPTION
TYROSINE