Disease relevance of Matk

• Functional analysis of Csk and CHK kinases in breast cancer cells [1].
• Matk/CHK is a potential tumour suppressor in colon carcinoma [2]
• Three independent superhybrid clones (CL 10B, Cl 10C, Cl 11A) isolated after backcross of the Cl 6d.6BU hybrid with a nontransformed Chinese hamster kidney cell line (CHK/AG) were able to produce infectious SV40 virus [3].

High impact information on Matk

• This enzyme is also named CHK, Ctk, BatK, Ntk and Hyl [4]
• Ntk: a Csk-related protein-tyrosine kinase expressed in brain and T lymphocytes [5].
• Firm evidence that Ntk is a Csk-related enzyme was provided by the observation that it phosphorylated a Src-related polypeptide on the inhibitory carboxyl-terminal tyrosine [5][6]
• In addition, Matk/CHK can employ a non-catalytic inhibitory mechanism to inhibit multiple active forms of Src family kinases. This mechanism involves direct binding of Matk/CHK to the active Src family kinases to form stable complexes. The binding alone is sufficient to inhibit the Src family kinase activity [7].
• The amino acid sequence of Ctk was found to possess 53% identity with mouse Csk, shared all the predicted structural features of Csk, and was capable of phosphorylating the carboxyl-terminal conserved tyrosine of Src family members [8].
• Interestingly, when mice received the in vivo antigen challenge of TNP-ovalbumin followed by restimulation, the Matk/CHK(-/-) lymph node and spleen cells produced significantly lower IFN-gamma levels compared with the respective wild-type cells [9].
• Moreover, Matk/CHK deficiency led to significantly higher pre-B cell colony formation following IL-7 stimulation [9].

Biological context of Matk

• Ctk and a closely related enzyme, nervous tissue and T-lymphocyte kinase (Ntk), are assembled by selective use of two of the exons [10].
• CHK significantly inhibited in vitro cell growth, transformation, and invasion induced upon HRG stimulation [1].
• Analysis of CSK homologous kinase (CHK/HYL) in hematopoiesis by utilizing gene knockout mice [11].
• The initially described phosphorylation sites of Src include an activating phosphotyrosine 416 that results from autophosphorylation, and an inhibiting phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase (Csk) and Csk homologous kinase [12].
• Tyr-568 has previously been identified as the binding site of the Src family of tyrosine kinases, the Csk-homologous kinase CHK, and the protein tyrosine phosphatase SHP-2 [13].
• In addition to Src family kinases, Matk/CHK can also phosphorylate other cellular proteins [14]. The optimal phosphorylation sequence of Matk/CHK has been defined by combinatorial peptide library screen as E-x-[Φ/E/D]-Y-Φ-x-Φ, where Φ and x represent hydrophobic residues and any residue, respectively [14].

Anatomical context of Matk

• Csk expression and kinase activity were abundant in normal human breast tissues, breast carcinomas, and breast cancer cell lines, whereas CHK expression was negative in normal breast tissues and low in some breast tumors and in the MCF-7 breast cancer cell line [1].
• This last finding suggested that the Ntk proteins can associate with the cytoskeleton [15].
• These results suggest that Ctk is involved in the regulation of neural function and differentiation of male germ cells through interactions with member(s) of the Src family kinases [16].
• Northern blotting and RT-PCR analyses showed that CHK/HYL was expressed in large spectrum of hematopoietic cells except for erythroid cells and brain [11].
• To inhibit SFKs, CSK and CHK need to translocate to the plasma membrane [17].
• Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma [18].

Associations of Matk with chemical compounds

• Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice [9].

Other interactions of Matk

• Role of SRC kinases in Neu-induced tumorigenesis: challenging the paradigm using Csk homologous kinase transgenic mice [19].
• This was thought to be due to the homologous kinase Csk that compensates for Matk/CHK [9].

References