Protein tyrosine kinase

Details Protein tyrosine kinase Protein tyrosine kinase

1993-06-30

1998-12-22

Wax, Robert A.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 231, 4353201, 4351723, 435194, C15N 1554

Patent

active

058521844

DESCRIPTION:

BRIEF SUMMARY
The present invention relates generally to a novel protein tyrosine kinase and to genetic sequences encoding same.
Protein tyrosine kinases (PTKs) are structurally well suited to a role introcellular signal transduction. Many growth factor receptors, for example, transduce the extracellular stimulus they receive through interaction with their cognate ligand via an intracellular tyrosine kinase domain. At least one of the non-receptor PTKs, namely LCK, is believed to mediate the transduction in T-cells of a signal from the interaction of a cell-surface protein (CD4) with a cross-linked anti-CD4 antibody.
The broader family of PTKs can be sub-divided on the basis of structural parameters of individual members. For example, the src family of PTKs now numbers 8 members (Marth et al., 1985; Nishizawa et al. 1986; Semba et al., 1986; Martinez et al., 1987; Sukegawa et al., 1987; Yamanishi et al., 1987; Hotzman et al., 1987; Dymecki et al., 1990), each with a characteristic complement of extra-catalytic domains, including an SH2, an SH3 domain and a variable ligand binding domain. It is clear that a process of gene duplication has taken place in this case, so that the evolutionarily successful thematic structure of this family can be employed in a variety of cellular contexts. Similarly PTK structural sub-families exist based around the PGF receptor and the CSF-1 receptor (reviewed in Wilks, 1990).
However, one feature in common with the aforementioned PTKs is that each kinase bears a single highly related "catalytic" domain.
In accordance with the present invention a protein tyrosine kinase is provided which is distinct from those previously known, in particular, the protein tyrosine kinase of the present invention is unique since it possesses more than one protein kinase catalytic domain. Furthermore, the kinase does not bear an SH2 domain. The novel protein tyrosine kinase of present invention represents a new subfamily or class of protein tyrosine kinase.
Accordingly, one aspect of the present invention is directed to an animal protein tyrosine kinase-like molecule comprising a polypeptide having multiple protein kinase catalytic domains but no SH2 domain.
Preferably, the polypeptide has two protein kinase catalytic domains.
Preferably, the animal is a mammal and is most preferably a human or a mouse.
Hereinafter, a protein having these characteristics will be referred to as a "JAK" (from JAnus Kinase: Janus, in Encyclopacdia Britannica (11Th Ed) Vol XV pp 155-156). The present invention is specifically exemplified using JAK1 and JAK2 from humans and mice. This is done, however, with the understanding that the present invention extends to the whole family of JAKs from all animals and to mutants, derivatives, analogues and homologues thereof. The term "protein tyrosine kinase-like molecule" (abbreviated herein to "PTK-like molecule") is used throughout the specification and claims to emphasise that the present invention encompasses all members of the JAK family and to their mutants, derivatives, analogues and homologues.
In accordance with the present invention, there is provided a PTK-like molecule. Preferably the molecule is in biological pure or in substantially pure and/or synthetic form. The purity of the preparation is characterized by a sample comprising at least 70% by weight, preferably at least 80% by weight and most preferably at least 90% by weight PTK-like molecule. Alternatively, where the purity of the enzyme preparation is not critical, the present invention also encompasses an impure PTK-like molecule preparation but which possesses a substantial amount of JAK activity.
The present invention is directed to a naturally occurring PTK-like molecule, biologically pure or substantially pure as hereinbefore defined and to derivatives, functional analogues and homologues thereof. Such derivatives include polypeptides having single or multiple amino acid substitutions, deletions and/or additions relative to the naturally occurring sequence. These derivatives, functional analogues and homologues also e

REFERENCES:
patent: 4543439 (1985-09-01), Frackelton
Firmbach-Kraft et al Oncogene (1990) 5:1329-36.
Wilks Proc. Nat. Acad Sci, USA (1989) 86 1603-1607.
Bernards. Oncogene (1991) 6 1185-1187.
Harpur et al. Oncogene (1992) 7: 1347-1353.
Wilks et al Mol. Cell. Biol. (1991) 11: 2057-2065.
Hanks, "The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains", vol. 241, pp. 42-52 (Jul. 1988).
Gaudette, "Effect of Genistein, A Tyrosine Kinase Inhibitor, On U46619--Induced Phosphoinositide Phosphorylation In Human Platelets", Biochem. Biophys. Res. Comm. vol. 170, No. 1, pp. 238-242 (Jul. 1990).
Koch, "SH2 and SH3 Domains: Elements That Control Interactions of Cytoplasmic Signaling Proteins", vol. 252, pp. 668-674 (May 1991.
Sadowski, "A Noncatalytic Domain Conserved among Cytoplasmic Protein-Tyrosine Kinases Modifies the Kinase Function and Transforming Activity of Fujinami Sarcoma Virus P130gag-fps", Mol. and Cell Biol. vol. 6, No. 12, pp. 4396-4408 (Dec. 1986).
Yarden, "Growth Factor Receptor Tyrosine Kinases", Ann. Rev. Biochem. vol. 57, pp. 443-478 (1988).

Affiliated with

Also associated with

Rating

Protein tyrosine kinase does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Protein tyrosine kinase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Protein tyrosine kinase will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2049357