Mammalian alpha-kinase proteins, nucleic acids and diagnostic and therapeutic uses thereof

An isolated nucleic acid encoding mammalian heart alpha kinase, wherein the nucleic acid is selected from the group consisting of:

• a. the DNA sequence of SEQ ID NO:
• 34;
• b. the DNA sequence of SEQ ID NO:
• 36;
• c. DNA sequences that hybridize to the sequence of subparts (a) or (b) under standard hybridization conditions;
• and
• d. DNA sequences capable of encoding the amino acid sequence encoded by the DNA sequences of subparts (a), (b) or (c).

An isolated nucleic acid encoding mammalian kidney alpha kinase, wherein the nucleic acid is selected from the group consisting of:

• a. the DNA sequence of SEQ ID NO:
• 30;
• b. the DNA sequence of SEQ ID NO:
• 32;
• c. DNA sequences that hybridize to the sequence of subparts (a) or (b) under standard hybridization conditions;
• and
• d. DNA sequences capable of encoding the amino acid sequence encoded by the DNA sequences of subparts (a), (b) or (c).

In particular, the invention provides an isolated nucleic acid encoding mammalian skeletal muscle alpha kinase, wherein the nucleic acid is selected from the group consisting of:

• a. the DNA sequence of SEQ ID NO:
• 38;
• b. DNA sequences that hybridize to the sequence of subpart (a) under standard hybridization conditions;
• and
• c. DNA sequences capable of encoding the amino acid sequence encoded by the DNA sequences of (a) or (b).

An isolated nucleic acid encoding mammalian lymphocyte alpha kinase, wherein the nucleic acid is selected from the group consisting of:

• a. the DNA sequence of SEQ ID NO:
• 40;
• b. DNA sequences that hybridize to the sequence of subpart (a) under standard hybridization conditions;
• and
• c. DNA sequences capable of encoding the amino acid sequence encoded by the DNA sequences of (a) or (b).

A unicellular host transformed with a recombinant DNA molecule comprising a DNA sequence or degenerate variant thereof, which encodes an alpha kinase, or a fragment thereof, selected from the group consisting of:

• a. the DNA sequence of (SEQ ID NO:
• 26);
• b. the DNA sequence of (SEQ ID NO:
• 28);
• c. the DNA sequence of (SEQ ID NO:
• 30);
• d. the DNA sequence of (SEQ ID NO:
• 32);
• e. the DNA sequence of (SEQ ID NO:
• 34);
• f. the DNA sequence of (SEQ ID NO:
• 36);
• g. the DNA sequence of (SEQ ID NO:
• 38);
• h. the DNA sequence of (SEQ ID NO:
• 40);
• i. DNA sequences that hybridize to any of the foregoing DNA sequences under standard hybridization conditions;
• and
• j. DNA sequences that code on expression for an amino acid sequence encoded by any of the foregoing DNA sequences;
• wherein said DNA sequence is operatively linked to an expression control sequence.

A method for detecting the presence or activity of an alpha kinase protein selected from the group of melanoma alpha kinase, kidney alpha kinase, heart alpha kinase, skeletal muscle alpha kinase and lymphocyte alpha kinase, wherein said alpha kinase is measured by:

• A. contacting a biological sample from a mammal in which the presence or activity of said alpha kinase is suspected with a binding partner of said alpha kinase under conditions that allow binding of said alpha kinase to said binding partner to occur;
• and
• B. detecting whether binding has occurred between said alpha kinase from said sample and the binding partner;
• wherein the detection of binding indicates that presence or activity of said alpha kinase in said sample.

A method for detecting the presence of an alpha kinase protein selected from the group of melanoma alpha kinase, kidney alpha kinase, heart alpha kinase, skeletal muscle alpha kinase and lymphocyte alpha kinase, wherein the alpha kinase is measured by:

• a. contacting a sample in which the presence or activity of an alpha kinase protein selected from the group of melanoma alpha kinase, kidney alpha kinase, heart alpha kinase, skeletal muscle alpha kinase and lymphocyte alpha kinase is suspected with an antibody to the said alpha kinase protein under conditions that allow binding of the alpha kinase protein to the binding partner to occur;
• and
• b. detecting whether binding has occurred between the alpha kinase protein from the sample and the antibody;
• wherein the detection of binding indicates the presence or activity of the alpha kinase protein in the sample.

A method of testing the ability of a drug or other entity to modulate the kinase activity of an alpha kinase protein selected from the group of melanoma alpha kinase, kidney alpha kinase, heart alpha kinase, skeletal muscle alpha kinase and lymphocyte alpha kinase which comprises:

• A. culturing a colony of test cells containing the alpha kinase protein;
• B. adding the drug or other entity under test;
• and
• C. measuring the kinase activity of said alpha kinase protein in the test cells, wherein when the amount of kinase activity in the presence of the modulator is greater than in its absence, the modulator is identified as an agonist or activator of the alpha kinase protein, whereas when the amount of kinase activity in the presence of the modulator is less than in its absence, the modulator is identified as an antagonist or inhibitor of the alpha kinase protein.