Computational and functional analysis of the putative SH2 domain in Janus Kinases.
Src homology 2 (SH2) domains interact in a highly specific manner with phosphorylated tyrosine residues on other signaling molecules. Protein tyrosine kinases (PTK) frequently contain SH2 domains, which often control signaling specificity. The Janus Kinases (JAKs) are a family of PTKs involved in signal transduction pathways mediated by various cytokines. Initial characterization of JAKs showed no identifiable SH2 domain. However, we have found substantial evidence supporting the existence of an SH2 domain in JAKs through the use of various web-based computational analysis programs. Predictive secondary and tertiary structures recognize an SH2 domain in JAKs. In addition, a three-dimensional homology model was constructed using the SH2 domains of Src tyrosine kinase and Syp tyrosine phosphatase as templates. These results, in conjunction with preliminary binding studies showing interactions with tyrosine phosphorylated proteins in activated splenocytes, suggest a functional role for this domain in JAKs.
Kampa
D
D
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19717, USA.
Burnside
J
J
D000595:Amino Acid Sequence; D000818:Animals; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012984:Software; D013601:T-Lymphocytes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains
D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3