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Gene Review

SIK1  -  salt-inducible kinase 1

Homo sapiens

Synonyms: MSK, SIK, SIK-1, SNF1LK, Salt-inducible kinase 1, ...
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Disease relevance of SNF1LK

  • Interestingly, the region encompassing the SNF1LK locus has been implicated in congenital heart defects often observed in patients with Down syndrome. snf1lk is also expressed in skeletal muscle progenitor cells of the somite beginning at 9.5 dpc [1].
  • HIV-1 p24 antigen was detected more frequently in CSF samples from demented (19/40) than normal (1/26) or mildly impaired (1/17) subjects and in 67% of individuals with significant dementia (MSK stages 2-4). p24 Antigen was detected less frequently in CSF from demented subjects on antiretroviral drugs than untreated demented individuals [2].
  • Medullary sponge kidney ( MSK ) is one of the entities which comprises a subclass of renal cystic disorders [3].
  • METHODS: We sent questionnaires to patients with SLE (n = 93) and controls with noninflammatory musculoskeletal disorders (MSK; n = 353) including osteoarthritis, fibromyalgia, and tendonitis [4].
  • RESULTS: The median doubling times were 101 days in the MLP and 144 days in the MSK, times that are somewhat shorter than those reported in published series of adenocarcinoma cases diagnosed outside screening, and only 5% had doubling times exceeding 400 days [5].

Psychiatry related information on SNF1LK

  • No patients developed AIDS dementia complex during the study; 3 patients developed minimal symptoms (MSK classification stage 0.5) [6].

High impact information on SNF1LK

  • Our analysis argued against most of the model-based hypotheses and instead identified a small number of novel candidate genes, including PFKFB2, a key regulator of glucose metabolism; ZBTB16, a putative transcription factor; and SNF1LK, a protein kinase implicated in cell-cycle regulation [7].
  • Salt-inducible kinase (SIK), one of the serine/threonine protein kinases, was transiently expressed in Y1 cells during the early phase of the ACTH/cAMP-dependent protein kinase (PKA)-mediated signal transduction [8].
  • Thus, members of the SIK family are emerging as important modulators of key processes such as steroid hormone biosynthesis by the adrenal cortex and insulin signaling in adipocytes [9].
  • Surprisingly, three of these genes encoded enzymes involved in carbohydrate metabolism (ADPglucose pyrophosphorylase, sucrose synthase and an SNF1-like kinase) [10].
  • Modulation of telomerase activity was investigated in the spontaneously immortalized SIK human epidermal cell line [11].

Chemical compound and disease context of SNF1LK


Biological context of SNF1LK

  • These two opposing signals are connected by the fact that SIK phosphorylates TORC and induces its nuclear export [13].
  • Patients with MSK had normal GFR, RPF, and capacity to dilute urine; however, their urine concentrating ability was diminished [3].
  • A specific set of learning outcomes has been defined, which will facilitate future informed education and practice development and provide a blueprint for a structured rheumatology MSK US curriculum and assessment process [14].
  • We show that synthetic peptides at two sites in the laminin B1 chain (the RGD and YIGSR sequences) inhibit angiogenesis, whereas a third site in the A chain, designated SIK-VAV, stimulates vessel and tumor cell growth [15].
  • These results suggest that the intracellular re-distribution of SIK in Y-1 cells may depend on the cAMP/PKA signaling pathway and has an important regulatory role in the ACTH-mediated steroidogenic gene expression [16].

Anatomical context of SNF1LK

  • Thus the spontaneously immortalized SIK line provides a useful model for study of telomerase modulation during the neoplastic progression of keratinocytes [11].
  • They reviewed 115 MSK US skills, comprising bone and soft tissue pathology, in seven joints regions of the upper and lower limbs, and rated their relative importance according to specific criteria [14].
  • The nuclear/cytosol re-distribution of GFP-SIK was also observed in forskolin- or 8-Br-cAMP-treated Y-1 cells, but not in Kin-7 cells [16].
  • When GFP-SIK was introduced into HeLa cells, the fluorescent signals were detected in the nucleus [16].
  • Possible involvement of salt-inducible kinase (SIK), a serine/threonine protein kinase first cloned from high K+-diet treated rat adrenal glands, in the regulation of steroidogenesis was investigated [16].

Associations of SNF1LK with chemical compounds

  • Salt-inducible kinase (SIK), a 776 amino acids-protein, contains a kinase domain in the NH2-terminal 278 amino acid residues, and the biological functions of its COOH-terminal half have yet to be clarified [17].

Other interactions of SNF1LK

  • Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade [13].

Analytical, diagnostic and therapeutic context of SNF1LK

  • BACKGROUND: A competency based approach to the education of rheumatologists in musculoskeletal ultrasonography (MSK US) ensures standards are documented, transparent, accountable, and defensible, with clear benefit to all stakeholders [14].
  • In addition to clinical application, 3T MR imaging has an important role for furthering translational research in MSK diseases through the development of new molecular and functional MR imaging techniques [18].
  • The diagnosis of medullary sponge kidney ( MSK ) is usually made as an incidental finding on pyelogram [19].


  1. snf1lk encodes a protein kinase that may function in cell cycle regulation. Stephenson, A., Huang, G.Y., Huang, G.Y., Nguyen, N.T., Reuter, S., McBride, J.L., Ruiz, J.C. Genomics (2004) [Pubmed]
  2. Cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) p24 antigen levels in HIV-1-related dementia. Royal, W., Selnes, O.A., Concha, M., Nance-Sproson, T.E., McArthur, J.C. Ann. Neurol. (1994) [Pubmed]
  3. Medullary sponge kidney and renal acidification defect. Higashihara, E., Nutahara, K., Tago, K., Ueno, A., Niijima, T. Kidney Int. (1984) [Pubmed]
  4. Close association of herpes zoster reactivation and systemic lupus erythematosus (SLE) diagnosis: case-control study of patients with SLE or noninflammatory nusculoskeletal disorders. Pope, J.E., Krizova, A., Ouimet, J.M., Goodwin, J.L., Lankin, M. J. Rheumatol. (2004) [Pubmed]
  5. Overdiagnosis in chest radiographic screening for lung carcinoma: frequency. Yankelevitz, D.F., Kostis, W.J., Henschke, C.I., Heelan, R.T., Libby, D.M., Pasmantier, M.W., Smith, J.P. Cancer (2003) [Pubmed]
  6. SPECT with 99mTc-HMPAO in subjects with HIV infection: cognitive dysfunction correlates with high uptake. Christensson, B., Ljungberg, B., Ryding, E., Svenson, G., Rosén, I. Scand. J. Infect. Dis. (1999) [Pubmed]
  7. Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia. Schmidt, S., Rainer, J., Riml, S., Ploner, C., Jesacher, S., Achmüller, C., Presul, E., Skvortsov, S., Crazzolara, R., Fiegl, M., Raivio, T., Jänne, O.A., Geley, S., Meister, B., Kofler, R. Blood (2006) [Pubmed]
  8. Salt-inducible kinase represses cAMP-dependent protein kinase-mediated activation of human cholesterol side chain cleavage cytochrome P450 promoter through the CREB basic leucine zipper domain. Doi, J., Takemori, H., Lin, X.Z., Horike, N., Katoh, Y., Okamoto, M. J. Biol. Chem. (2002) [Pubmed]
  9. Salt-inducible kinase in steroidogenesis and adipogenesis. Okamoto, M., Takemori, H., Katoh, Y. Trends Endocrinol. Metab. (2004) [Pubmed]
  10. Novel marker genes for early leaf development indicate spatial regulation of carbohydrate metabolism within the apical meristem. Pien, S., Wyrzykowska, J., Fleming, A.J. Plant J. (2001) [Pubmed]
  11. Telomerase deregulation in immortalized human epidermal cells: modulation by cellular microenvironment. Rea, M.A., Rice, R.H. Int. J. Cancer (2001) [Pubmed]
  12. Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia - case report. Andersson, L.M., Hagberg, L., Rosengren, L., Fuchs, D., Blennow, K., Gissl??n, M. BMC Infect. Dis. (2006) [Pubmed]
  13. Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade. Katoh, Y., Takemori, H., Lin, X.Z., Tamura, M., Muraoka, M., Satoh, T., Tsuchiya, Y., Min, L., Doi, J., Miyauchi, A., Witters, L.A., Nakamura, H., Okamoto, M. FEBS J. (2006) [Pubmed]
  14. Ultrasonography for rheumatologists: the development of specific competency based educational outcomes. Brown, A.K., O'Connor, P.J., Roberts, T.E., Wakefield, R.J., Karim, Z., Emery, P. Ann. Rheum. Dis. (2006) [Pubmed]
  15. The role of basement membrane in angiogenesis and tumor growth. Grant, D.S., Kibbey, M.C., Kinsella, J.L., Cid, M.C., Kleinman, H.K. Pathol. Res. Pract. (1994) [Pubmed]
  16. SIK (Salt-inducible kinase): regulation of ACTH-mediated steroidogenic gene expression and nuclear/cytosol redistribution. Lin, X., Takemori, H., Doi, J., Katoh, Y., Okamoto, M. Endocr. Res. (2000) [Pubmed]
  17. Roles of several domains identified in the primary structure of salt-inducible kinase (SIK). Horike, N., Takemori, H., Katoh, Y., Doi, J., Okamoto, M. Endocr. Res. (2002) [Pubmed]
  18. Musculoskeletal imaging at 3T: current techniques and future applications. Mosher, T.J. Magnetic resonance imaging clinics of North America. (2006) [Pubmed]
  19. Differential diagnosis of medullary sponge kidney. Zawada, E.T., Sica, D.A. South. Med. J. (1984) [Pubmed]
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