The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (
SH2/
SH3) and the presence of up to seven
JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a
pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of the JH1 domain.[7][8]
Loss of Jak2 is lethal by embryonic day 12 in mice.[9]
JAK2orthologs[10] have been identified in all
mammals for which complete genome data are available.
^Brooks AJ, Dai W, O'Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, et al. (2014). "Mechanism of activation of protein kinase JAK2 by the growth hormone receptor". Science. 344 (6185): 1249783.
doi:
10.1126/science.1249783.
PMID24833397.
S2CID27946074.
^Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffé M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (November 1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia". Science. 278 (5341): 1309–12.
Bibcode:
1997Sci...278.1309L.
doi:
10.1126/science.278.5341.1309.
PMID9360930.
^Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (July 1993). "JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin". Cell. 74 (2): 227–36.
doi:
10.1016/0092-8674(93)90414-L.
PMID8343951.
S2CID37503350.
^Hellgren G, Jansson JO, Carlsson LM, Carlsson B (June 1999). "The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver". Growth Hormone & IGF Research. 9 (3): 212–8.
doi:
10.1054/ghir.1999.0111.
PMID10502458.
^Yamamoto K, Shibata F, Miura O, Kamiyama R, Hirosawa S, Miyasaka N (April 1999). "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus". Biochemical and Biophysical Research Communications. 257 (2): 400–4.
doi:
10.1006/bbrc.1999.0479.
PMID10198225.
^
abcFuhrer DK, Yang YC (July 1996). "Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11". Biochemical and Biophysical Research Communications. 224 (2): 289–96.
doi:
10.1006/bbrc.1996.1023.
PMID8702385.
^Maegawa H, Kashiwagi A, Fujita T, Ugi S, Hasegawa M, Obata T, Nishio Y, Kojima H, Hidaka H, Kikkawa R (November 1996). "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates". Biochemical and Biophysical Research Communications. 228 (1): 122–7.
doi:
10.1006/bbrc.1996.1626.
PMID8912646.
^
abMasuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–46.
doi:
10.1006/bbrc.1997.7484.
PMID9344848.
The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (
SH2/
SH3) and the presence of up to seven
JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a
pseudokinase domain, has since been found to be catalytically active, albeit at only 10% that of the JH1 domain.[7][8]
Loss of Jak2 is lethal by embryonic day 12 in mice.[9]
JAK2orthologs[10] have been identified in all
mammals for which complete genome data are available.
^Brooks AJ, Dai W, O'Mara ML, Abankwa D, Chhabra Y, Pelekanos RA, et al. (2014). "Mechanism of activation of protein kinase JAK2 by the growth hormone receptor". Science. 344 (6185): 1249783.
doi:
10.1126/science.1249783.
PMID24833397.
S2CID27946074.
^Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffé M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (November 1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia". Science. 278 (5341): 1309–12.
Bibcode:
1997Sci...278.1309L.
doi:
10.1126/science.278.5341.1309.
PMID9360930.
^Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (July 1993). "JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin". Cell. 74 (2): 227–36.
doi:
10.1016/0092-8674(93)90414-L.
PMID8343951.
S2CID37503350.
^Hellgren G, Jansson JO, Carlsson LM, Carlsson B (June 1999). "The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver". Growth Hormone & IGF Research. 9 (3): 212–8.
doi:
10.1054/ghir.1999.0111.
PMID10502458.
^Yamamoto K, Shibata F, Miura O, Kamiyama R, Hirosawa S, Miyasaka N (April 1999). "Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus". Biochemical and Biophysical Research Communications. 257 (2): 400–4.
doi:
10.1006/bbrc.1999.0479.
PMID10198225.
^
abcFuhrer DK, Yang YC (July 1996). "Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11". Biochemical and Biophysical Research Communications. 224 (2): 289–96.
doi:
10.1006/bbrc.1996.1023.
PMID8702385.
^Maegawa H, Kashiwagi A, Fujita T, Ugi S, Hasegawa M, Obata T, Nishio Y, Kojima H, Hidaka H, Kikkawa R (November 1996). "SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates". Biochemical and Biophysical Research Communications. 228 (1): 122–7.
doi:
10.1006/bbrc.1996.1626.
PMID8912646.
^
abMasuhara M, Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (October 1997). "Cloning and characterization of novel CIS family genes". Biochemical and Biophysical Research Communications. 239 (2): 439–46.
doi:
10.1006/bbrc.1997.7484.
PMID9344848.