The role of the Src Homology-2 domain containing protein B (SHB) in β cells.
This review will describe the SH2-domain signaling protein Src Homology-2 domain containing protein B (SHB) and its role in various physiological processes relating in particular to glucose homeostasis and β cell function. SHB operates downstream of several tyrosine kinase receptors and assembles signaling complexes in response to receptor activation by interacting with other signaling proteins via its other domains (proline-rich, phosphotyrosine-binding and tyrosine-phosphorylation sites). The subsequent responses are context-dependent. Absence of Shb in mice has been found to exert effects on hematopoiesis, angiogenesis and glucose metabolism. Specifically, first-phase insulin secretion in response to glucose was impaired and this effect was related to altered characteristics of focal adhesion kinase activation modulating signaling through Akt, ERK, β catenin and cAMP. It is believed that SHB plays a role in integrating adaptive responses to various stimuli by simultaneously modulating cellular responses in different cell-types, thus playing a role in maintaining physiological homeostasis.
Department of Medical Cell BiologyUppsala University, PO Box 571, Husargatan 3, SE-75123 Uppsala, Sweden Michael.welsh@mcb.uu.se.
Michael
M
Welsh
Department of Medical Cell BiologyUppsala University, PO Box 571, Husargatan 3, SE-75123 Uppsala, Sweden.
Maria
M
Jamalpour
Department of Medical Cell BiologyUppsala University, PO Box 571, Husargatan 3, SE-75123 Uppsala, Sweden.
Guangxiang
G
Zang
Department of Medical Cell BiologyUppsala University, PO Box 571, Husargatan 3, SE-75123 Uppsala, Sweden.
Björn
B
Åkerblom
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D011518:Proto-Oncogene Proteins; C490081:SHB protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
immune system; insulin secretion; islet cells; signal transduction; vascular